JP2020203105A - Chemical engines and methods for their use, especially in injection of highly viscous fluids - Google Patents

Abstract

To provide novel formulations and designs of chemical engines and delivery technologies employing the chemical engines.SOLUTION: A syringe 1300 includes a barrel 1310 having an internal space divided into three separate chambers. The syringe begins at a top end part 1302 of the barrel and includes a reagent chamber 1320, a reaction chamber 1330, and a fluid chamber 1340. These three chambers are coaxial and, herein, is depicted so as to have a cylindrical shape. In the embodiment, the barrel of the syringe is formed by two different portions. A first portion 1380 includes a side wall 1312 forming the reaction chamber and providing a space 1313 for the reagent chamber. For a push button, the side wall is opened at the top end part. The fluid chamber is made of a second portion 1390 that may be attached to the first portion.SELECTED DRAWING: Figure 19

Description

Cross-reference to related applications This application is a US provisional patent application filed on October 12, 2012, No. 61/713.
Claims the priority of US Provisional Patent Application Nos. 236 and 61 / 713,250 and US Provisional Patent Application Nos. 61 / 817,312 filed on April 29, 2013.

The present invention relates to a technique for generating gas by a chemical reaction. The forces created by the released gas can be used to power useful processes. Chemical reactions avoid many problems related to combustion, not combustion. Instead, chemical reactions are usually involved in the generation of CO ₂ from bicarbonate (HCO ₃ ). Generally, the present technology is simply referred to as ChemEngine®, as is known for chemical institutional technology, or technology developed by the Battelle Memorial Institute. The present invention is particularly useful for the delivery of protein therapies.

Protein therapy is an emerging area of drug therapy that can treat a wide range of diseases. Due to its large size and poor stability, the protein must be delivered by parenteral delivery methods such as injection or infusion. For patients suffering from chronic illnesses that require regular treatment, the trend is towards self-administration by subcutaneous injection, for example in the administration of insulin by diabetics. A typical subcutaneous injection involves delivery of 1 mL of formulation in less than 20 seconds, but sometimes up to 3 mL. Subcutaneous injection can be performed on several devices, including syringes, automatic injectors and pen-type injectors.

The transition of therapeutic protein preparations from intravenous delivery to syringe-like injection devices is an easy, reliable and minimal pain method for the challenges associated with delivering high concentrations of high molecular weight molecules. Need to be dealt with in. At that time, the drip bag is typically 1
While having a volume of liters, the standard volume of syringes ranges from 0.3 ml to 25 ml. Therefore, depending on the drug, the concentration may need to be increased by a factor of 40 or more to deliver the same amount of therapeutic protein. further,
Injection treatment is advancing towards smaller needle diameters and faster delivery times for the purposes of patient comfort and compliance.

Delivery of protein therapy is also difficult due to the high viscosity associated with these therapeutic formulations and the strong force required to push these formulations through parenteral devices. 20 cm pores (c
Formulations with absolute viscosities above P), and especially above 40-60 centipores (cP),
Delivery by a conventional spring-loaded automatic syringe is very difficult for multiple reasons. Structurally, the occupied area of the spring for the amount of pressure delivered is fixed in a relatively large and distinctive shape, which reduces the design flexibility of the delivery device. Second, automatic syringes are usually made of plastic parts. However, a large amount of energy must be stored in the spring to reliably deliver the viscous fluid. This can damage plastic parts due to creep, which is a characteristic of plastic parts that deform permanently under stress. Automatic syringes typically operate by using a spring to push an internal component containing the needle toward the outer edge of the syringe housing. Due to the high pressurization required to inject the viscous fluid, there is a risk of destroying the syringe when the internal components collide with the housing. In addition, shock-related sounds can cause patient anxiety and reduce future medication compliance. The generated pressure vs. time profile of these spring-loaded automatic syringes cannot be easily changed, which prevents the user from fine-tuning the pressure to meet their delivery needs.

The forces required to deliver a given formulation are needle diameter (d), needle length (L), formulation viscosity (μ).
It depends on several factors, including volumetric flow (Q). In the simplest approximation (without considering the frictional force between the plunger and the barrel), the force is related to the pressure drop (ΔP) multiplied by the cross-sectional area of the plunger (A). The pressure drop (ΔP) of the fluid in the laminar flow through the needle can be described by the Hagen-Poiseuille equation.

In the syringe, the force is provided by the user. Reasonable finger strength is less than 15-20 N for a healthy patient population and somewhat lower for patients with limited dexterity, such as older patients or patients with rheumatoid arthritis or multiple sclerosis. Conceivable. In a typical automatic syringe, the force is provided by a spring. The force provided by the spring decreases linearly with displacement, and the spring must be selected so that sufficient force is available to sustain the injection. Viscosities above 20 cP are difficult to deliver in a reasonable amount of time with a typical spring-loaded automatic syringe.
-Breakage of the plastic part holding the compressed spring (large stored energy causes creep)
・ Syringe damage (high initial force)
Incomplete doss delivery due to stall (insufficient final force)
Other energy sources are considered for inflexible automatic syringes in device design, including large occupied area of springs. One source is the use of effervescent reactions that generate demand-type pressure. "Development of an On-D
emand, Generic, Drug-Delivery System, 19
The Office of Naval Reserve, entitled "85"
A study funded by rve) (SoRI-EAS-85-746) described the use of bicarbonate mixed with an acid to generate CO _2, which can drive the slow delivery of drug fluids. These devices were intended for slow, long-term delivery in excess of 24 hours.
Bottger and Bobst have described the use of syringes to deliver fluids using chemical reactions (US Patent Application Publication No. 2011/0092906). Good et al.
"An effect effervescent reaction micropump for
"Portable microfluidic systems", Lab Chip,
In 2006, pages 659-666 described formulations for micropumps with various concentrations of tartaric acid and sodium bicarbonate and different sizes of sodium bicarbonate particles. However, their invention provides delivery in a manner in which the firing power increases exponentially over time. Prior art chemical institutions provide appropriate delivery, especially when the effect of volume expanding in the piston is not negligible, such as when reagent volume is minimized to minimize the area occupied by the engine and the amount of overshoot. (If it does not occupy the expanding volume, the chemical institution can stall during delivery as the spring stalls).

The present invention provides a solution to the aforementioned problems by adopting improvements to chemical institution technology. In a particularly preferred embodiment, a process and apparatus in which a chemical institution can be used to comfortably and rapidly self-administer a viscous fluid with a relatively small syringe is described. These processes and devices can be used to deliver high concentration proteins or other high viscosity pharmaceutical formulations.

U.S. Patent Application Publication No. 2011/0092906

Navy Reserve Room, "Development of an On-Demand, Generic, Drug-Delivery System, 1985" Good et al., "An effectence reaction micropump for portable microfluidic systems", Lab Chip, 2006, pp. 659-666.

The present invention provides chemical institutions and methods of using chemical institutions to move fluids. The present invention also includes a method of creating a chemical institution.

In a first aspect, the invention comprises a closed container containing acid, bicarbonate, water and plunger and a mechanism adapted to mix acid, water and bicarbonate and a constant nominal back pressure of 40 N. in the molar ratio of the measured at least power density or sodium bicarbonate and citric acid 50,000W / ^{m 3} is 3: 1 and at least as compared to a control having a concentration of in _{H 2} O 403mg citric acid 1g It provides a chemical institution further characterized by an output density of a ratio of .4.

Considering the various factors described herein, it is not possible to define the whole invention by other means, so it is necessary to characterize the chemical institution by power density. No predetermined level of power density was obtained with the preceding equipment, and the claimed level of power density was not previously confirmed as desirable or achievable. This feature provides the ease of holding a powered syringe that is more comfortable than a conventional spring-loaded automatic syringe or the gas syringe described above, has a lower risk of breakage and delivers viscous solutions. It brings together so many technical advantages such as. The claimed features have the additional advantages of ease of measurement and high accuracy of the measured values.

In some preferred embodiments, at least 50 wt% bicarbonate is solid. Surprisingly, potassium bicarbonate has been found to provide a faster reaction than sodium bicarbonate and generate more CO ₂ under the same conditions otherwise. Therefore, in a preferred embodiment, the chemical institution contains at least 50 wt% potassium bicarbonate. Preferably, the acid is citric acid, and in some preferred embodiments, the citric acid is soluble in water and may provide an improved output density of solid potassium carbonate and citric acid in solution. In some preferred embodiments, the closed container contains 1.5 mL or less of liquid. In some preferred embodiments, the closed container has a total internal volume prior to mixing the acid and carbonate, or 2 mL or less. In some embodiments, the acid and bicarbonate are present as solids and the water is separated from the acid and bicarbonate.

Formulations for chemical institutions may be improved by the addition of convective agents. An improved pressure profile can also be provided if the bicarbonate contains a solid mixture of at least two particle morphologies.

The power density is typically used to describe the potential characteristics of a chemical institution and, less commonly, can be used to describe a system that has undergone a chemical reaction. In a preferred embodiment, the displacement of the plunger or flexible wall in the chemical engine is acid, carbonate and solvent (water).
It starts within 2 seconds, more preferably within 1 second of the moment when the chemicals are mixed, and this moment is the moment when the chemical institution starts.

In another embodiment, the present invention comprises a closed container comprising an acidic solution containing an acid dissolved in water and a bicarbonate and a plunger from which the acidic solution is separated from the solid bicarbonate, and an opening disposed within the closed container. Provided is a chemical institution comprising, following the initiation, with a conduit configured such that at least a portion of the acidic solution is pushed through at least a portion of the opening. Preferably, the bicarbonate is in the form of particulates and the conduit is a tube with one end that is placed within the solid bicarbonate so that it contacts the solid bicarbonate microparticles as the solution is pushed through the opening. Be prepared. In some preferred embodiments, at least a portion of the bicarbonate is placed inside the conduit in solid form. In some embodiments, the spring is configured to push the acidic solution through the conduit.

In some preferred embodiments of any aspect of the invention, the chemical institution is 2 ml or less, 1.5 ml or less in some embodiments, 1.0 ml or less in some embodiments and some embodiments. Has an internal volume in the range of 0.3 ml to 2 ml, 0.3 ml to 1.5 ml, 0.5 ml to 1.5 ml or 0.7 ml to 1.4 ml.

In another embodiment, the invention mixes an acidic solution containing an acid dissolved in water and a closed container with potassium bicarbonate and a plunger from which the acidic solution is separated from potassium bicarbonate, and the acidic solution and potassium bicarbonate. To provide a chemical institution with a mechanism adapted as such. In some embodiments, potassium bicarbonate is mixed with sodium bicarbonate. The molar ratio of potassium: sodium in bicarbonate is 100: 0, or at least 9, or at least 4, or at least 1, and in some embodiments at least 0.1, in some embodiments 0. It ranges from 1 to 9, and in some embodiments 0.5 to 2.

In a further embodiment, the invention comprises an acidic solution containing an acid dissolved in water, a closed container with solid bicarbonate particles and a solid particle convection agent and a plunger from which the acidic solution is separated from the solid bicarbonate, and an acidic solution. And provide a chemical institution with a mechanism adapted to mix solid bicarbonate. Solid particle convection agent is 5 per ml of mixed solution
A range of concentrations chosen to keep less than 0 mg and all other variable amounts constant, the first 5 seconds of CO ₂ generation mixed with acidic solution and solid bicarbonate is the particle convection agent per ml. Earlier range of CO ₂ generation in the presence of 50 mg, or m of mixed solution
It is present in a concentration range of 5 mg to 25 mg per l. In some embodiments, it is 5 mg to 15 mg or 5 mg to 10 mg per ml of the mixed solution.

The term "mixed solution" means the volume of liquid after the acidic solution and solid bicarbonate have been mixed. The term "solid bicarbonate" means that some liquid phase (typically an aqueous phase) may be present with the bicarbonate, but at least some solid bicarbonate is present. In some preferred embodiments, the bicarbonate is present at least 10% as a solid in the chemical institution prior to compounding with an acidic solution, and in some embodiments at least 5 as a solid
It is present at 0%, at least 90% or substantially 100%.

The term "solid convection agent" has lower solubility than solid bicarbonate under conditions present within a chemical engine (or in the case of unreacted chemical institutions, defined by standard temperature and pressure). Solid microparticles, preferably dissolved at least 2 times slower than solid bicarbonate, more preferably at least 10 times slower than solid bicarbonate, and in some embodiments at least 100 times slower. Point to. A "solid convection agent" has a density measured at ambient pressure by a mercury intrusion method, preferably at least 5%, more preferably at least 10% different from water or solution in which the convection agent is dispersed. The "solid convection agent" is preferably at least 1.05 g / ml.
, More preferably at least 1.1 g / ml, and in some embodiments at least 1.
It has a density of 2 g / ml, and in some embodiments ranging from 1.1 to 1.5 g / ml. Alternatively, the "solid convection agent" is lower than water, eg 0.95 g / ml or less,
It can have a density of 0.9 g / ml or less and 0.8 to 0.97 mg / ml in some embodiments. In a preferred embodiment, the convection agent is used in a non-supersaturated system and
This is typically the case in short time scale systems such as automatic syringe operation over 1 minute or less, preferably 30 seconds or less, more preferably 20 seconds or less, and even more preferably 10 seconds or 5 seconds or less. Therefore, the diatomaceous earth preparations of the present invention differ from the LeFavre system of US Pat. No. 4,785,972, which uses large amounts of diatomaceous earth to serve as a nucleating agent in supersaturated solutions over large time scales. The present invention utilizes a convection agent for a short period of time in which more than 50% of bicarbonate (more preferably at least 70% or at least 90%) is converted to gaseous carbon dioxide within a short time scale of 1 minute or less. Includes methods of operating a range of chemical institutions. Preferably, diatomaceous earth or other convective agent, optimal CO ₂ emissions from supersaturated systems which are designed to release a gaseous CO ₂ in CO ₂ which is formed in the solution over longer than 30 minutes At least 50% by weight than would be used to
Present in low concentration.

In another embodiment, the present invention comprises a closed container, an acidic solution and a solid bicarbonate, comprising an acidic solution containing an acid dissolved in water and a solid bicarbonate particle and a plunger, the acidic solution being separated from the solid bicarbonate. Provided is a chemical institution comprising a mechanism adapted to mix with, wherein the solid bicarbonate particles contain a mixture of particle morphology. In some embodiments, the solid bicarbonate particles are at least two different sources, a first source and a second source, the first source being one or more. Measured by the time required for complete dissolution of a solution evenly stirred with the following characteristics (mass average particle size, surface area per mass and / or solvent in a chemical institution (typically water)) into a 1 mol solution. 20C in water) is derived from a first source and a second source that differ by at least 20% from the second source.

In a further embodiment, the invention is a closed container containing an acid solution and bicarbonate containing an acid dissolved in water and a plunger, wherein the acidic solution is separated from the bicarbonate and the acidic solution and bicarbonate in the container. The salt defines the potential power density, the plunger separates the closed container from the chemical compartment, the step of providing the closed container, the acidic solution and bicarbonate react to generate CO ₂ and power the plunger. This plunger in turn pushes the liquid chemicals from the syringe, the pressure in the vessel reaches its maximum within 10 seconds after the start, and after 5 minutes, the potential output density is less than 20% of the initial potential output density. And after 10 minutes, the pressure in the closed container is 5 of the maximum pressure.
Provided is a method of injecting a liquid chemical from a syringe comprising the step of mixing an acidic solution and bicarbonate in a closed container, which is 0% or less. In some preferred embodiments, the closed vessel further comprises a CO ₂ remover that removes CO ₂ at least 10 times slower than the maximum rate at which CO ₂ is generated in the reaction.

A plunger at the upper end, and a reagent chamber with a one-way valve at the lower end, a reaction chamber with a one-way valve at the upper end and a piston at the lower end, and an upper end that allow the one-way valve to exit the reagent chamber. A device for delivering a fluid by a chemical reaction, comprising a fluid chamber with a piston in the piston, which increases the volume of the reaction chamber and decreases the volume of the fluid chamber in response to the pressure generated in the reaction chamber. A device that works in this way is disclosed in some embodiments.

In any of the aspects of the invention, the device or method can be characterized by one or more of the following features: The reaction chamber preferably has a volume of up to 1.5 cm ³ , and in some embodiments up to 1.0 cm ³ . Preferably, the fluid chamber has an absolute viscosity of about 5 centipoise to about 1000 cmpoise, or at least 20, preferably at least 40.
Centipores, in some embodiments, include high viscosity fluids having viscosities in the range of 20-100 cP. The reagent chamber may contain a solvent and / or bicarbonate or an acid dissolved in the solvent. The solvent preferably comprises water. In some preferred embodiments, the reaction chamber may contain a dry acid powder and a mold release agent. In some embodiments, the acid powder is citrate and the release agent is sodium chloride. Alternatively, the reaction chamber may contain at least one chemical reagent or at least two chemical reagents that react with each other to generate gas. The reaction chamber may further contain a release agent.

In some embodiments, the upper chamber may contain a solvent. The lower chamber may contain at least two chemical reagents that react with each other to generate gas. The lower chamber may contain, for example, bicarbonate powder and acid powder.

The device may include a push surface at the lower end of the reaction chamber, a stopper at the upper end of the fluid chamber, and a piston containing a rod connecting the push surface to the stopper. The piston is 1 of the plunger
Of the two types, plungers often do not include a rod that connects the push surface to the stopper.

The plunger may include a thumb rest as well as a pressure lock that locks the plunger in place in cooperation with the upper chamber after being pressed. The pressure lock may be in close proximity to the thumb rest and cooperates with the upper surface of the upper chamber. Plungers containing thumb rests may be referred to as starting plungers as they are often used to create a mixture of acids and carbonates in solution.

In some preferred embodiments, the chemical engine relative to each other such that the volumes of the lower chamber, the one-way valve and the lower chamber, defined by a one-way valve, a continuous side wall and a piston, change only through the movement of the piston. It may have a side wall that is fixed.

In a preferred embodiment, the upper, lower and fluid chambers are cylindrical and coaxial. Upper room,
The lower chamber and fluid chamber may be separate parts that are connected to make the device. The one-way valve may supply the balloon in the lower chamber where the balloon pushes the piston. Occasionally, either the upper chamber or the lower chamber contains encapsulated reagents.

In various embodiments, an upper chamber with a seal at the lower end, a lower chamber with a port at the upper end, a ring of teeth at the upper end with teeth directed to the seal of the upper chamber, a piston at the lower end, and an upper end. A device for delivering a fluid by a chemical reaction, comprising a fluid chamber with a piston in the upper chamber, which moves axially with respect to the lower chamber, and the piston has an increased volume of the reaction chamber and a fluid chamber. A device is also described that moves in response to the pressure generated in the lower chamber to reduce the volume of the.

The piston may include a head and a balloon that communicate with the port. A ring of teeth may surround the port. The upper chamber may proceed within the barrel of the device. Sometimes the upper chamber is the lower end of the plunger. The plunger may include a pressure lock that locks the upper chamber in place in cooperation with the top of the device after being pressed. Alternatively, the top of the device may include a pressure lock that, in cooperation with the top surface of the upper chamber, locks the upper chamber in place when sufficiently moved towards the lower chamber.

The fluid chamber may contain a highly viscous fluid having a viscosity of at least 5 or at least 20 or at least 40 centipores. The upper chamber may contain a solvent. The lower chamber may contain at least two chemical reagents that react with each other to generate gas. Sometimes the upper room,
The lower chamber and the fluid chamber are separate parts that are connected to make the device. In yet other embodiments, either the upper chamber or the lower chamber comprises encapsulated reagents.

Upper chamber, lower chamber with piston at lower end, fluid chamber with piston at upper end, shaft passing through upper chamber, stopper at lower end of shaft, upper chamber and lower chamber in cooperation with pedestal A device for delivering fluid by a chemical reaction with a stopper and a plunger with a thumb rest at the upper end of the shaft to separate the stopper from the pedestal by pulling the plunger to separate the upper and lower chambers. A device is also described herein that causes fluid communication between the pistons and moves the piston to increase the volume of the reaction chamber and decrease the volume of the fluid chamber in response to the pressure generated in the lower chamber.

The present disclosure is a device for delivering a fluid by a chemical reaction, the second compartment containing a first compartment and a solvent containing at least two dry chemical reagents capable of reacting with each other to generate gas.
A reaction chamber divided by a partition into a first compartment and a second compartment, and a fluid chamber having a discharge port are provided, and the fluid in the fluid chamber responds to the pressure generated in the reaction chamber. It also concerns the equipment that exits through the outlet.

The pressure generated in the reaction chamber can act on the piston or plunger at one end of the fluid chamber to allow the fluid to exit through the outlet of the fluid chamber.

In some embodiments, the reaction chamber comprises a flexible wall in close proximity to the fluid chamber, and the fluid chamber is a flexible side wall of the fluid chamber where the pressure generated in the reaction chamber expands the flexible wall. Is formed from the flexible sidewalls to squeeze and thus push the fluid out through the outlet.

The reaction chamber and fluid chamber may be surrounded by a housing. Occasionally, the reaction chamber and fluid chamber are adjacent within the housing. In another embodiment, the needle extends from the bottom of the housing to fluidly connect to the outlet of the fluid chamber, and the reaction chamber is located at the top of the fluid chamber.

The reaction chamber may be defined by a one-way valve, side wall and plunger in which the one-way valve and side wall are fixed relative to each other so that the volume of the reaction chamber changes only through the movement of the plunger.

A reaction chamber having first and second ends, a plunger at the first end of the reaction chamber, and a reaction chamber in which the plunger acts in response to the pressure generated in the reaction chamber. Devices for distributing fluid by chemical reaction, including a one-way valve at the second end of the reaction chamber that allows entry, are also disclosed in various embodiments.

The device may include a reagent chamber on the opposite side of the one-way valve. The reagent chamber may contain a solvent and a bicarbonate powder dissolved in the solvent. The solvent may include water. The device may further include a plunger at the end of the reagent chamber opposite the one-way valve. The plunger may lock the starting plunger in place in cooperation with the reagent chamber after being pressed.

For delivering fluid by a chemical reaction with a reagent chamber, a barrel divided into a reaction chamber and a fluid chamber by a one-way valve and a piston (or other type of plunger), and a start plunger at one end of the reagent chamber. A device in which a one-way valve is located between the reagent chamber and the reaction chamber, and a piston (or other type of plunger) is movable to change the volume ratio between the reaction chamber and the fluid chamber. An apparatus is also disclosed in various embodiments, wherein the piston separates the reaction chamber from the fluid chamber.

The present disclosure is a barrel containing a reaction chamber and a fluid chamber separated by a movable piston;
It also relates to a device for delivering a fluid by a chemical reaction, which comprises a heat source for heating the reaction chamber. The reaction chamber may contain at least one chemical reagent that produces gas when exposed to heat. At least one chemical reagent may be 2,2'-azobisisobutyronitrile. The generated gas may be nitrogen gas.

The present disclosure is a barrel containing a reaction chamber and a fluid chamber separated by a movable piston.
Also described are devices for delivering fluid by chemical reaction, including a light source that illuminates the reaction chamber. The reaction chamber may contain at least one chemical reagent that produces gas when exposed to light. At least one chemical reagent may contain silver chloride.

The initiation of the gas generation reaction in a chemical institution may be carried out by dissolving at least two different chemical reagents in a solvent. At least two chemical reagents may include a chemical compound having a first dissolution rate and a second chemical compound having a different dissolution rate. The dissolution rate can be varied by varying the surface area of the chemical compound or by encapsulating the chemical compound in a coating to obtain different dissolution rates.

The pressure-to-time profile from gas generation may include a burst in which the rate of gas generation increases faster than the initial generation of gas.

The reaction chamber contains a pre-dissolved bicarbonate (or pre-dissolved acid) that is added to the reaction chamber from the reagent chamber opposite the one-way valve for the solvent to initiate the reaction. It may contain a dry acid reagent. The reaction chamber may further contain a release agent such as sodium chloride. The solvent may include water. In some preferred embodiments, the dry acid reagent is citric acid powder or acetic acid powder. The gas produced is preferably carbon dioxide.

The reagent chamber is located inside the push button member at the top of the barrel, the barrel including the reagent chamber, reaction chamber and fluid chamber, the plunger that separates the reagent chamber from the reaction chamber, starts when the push button member is pressed. A device for delivering fluid by a chemical reaction with a spring urged to push the plunger into the reagent chamber, and a piston that separates the reaction chamber from the fluid chamber, with the piston moving in response to the pressure generated in the reaction chamber. Is also described herein. The push button member is
It may include a side wall closed by a contact surface at the outer end, an edge extending outward from the inner end of the side wall, and a sealing member close to the central portion on the outer surface of the side wall. The barrel may include an inner stop surface that engages the edge of the pushbutton member.

The starting plunger may include a central body with a lug extending radially from it and an inner end sealing member that engages the side walls of the reaction chamber. The inner surface of the pushbutton member may include a path for the lug.

The reaction chamber may be divided into a mixing chamber and an arm by an internal radial surface, an internal radial surface having an orifice and a piston located at the end of the arm.

As a general feature, the reaction chamber sometimes includes a gas permeable filter that covers an orifice that allows the gas to escape after the plunger moves to push the fluid out of the fluid chamber. This feature provides an excess gas release.

The barrel may be formed from a first portion and a second portion, which are a first portion containing a reagent chamber and a reaction chamber and a second portion containing a fluid chamber. The present invention includes a method of making a syringe or a syringe component with a syringe comprising an assembly of first and second parts.

In different embodiments, a reagent chamber with a unidirectional valve at the lower end, a unidirectional valve at the upper end, which is a unidirectional valve that allows the activator at the upper end and the reagent to exit the reaction chamber when activated. A reaction chamber operably connected to the reagent chamber with means for receiving the piston at the valve and lower end, and a fluid chamber operably connected to the reaction chamber with means for receiving the piston at the upper end. An injection device for delivering a reagent fluid to a patient using the pressure generated by an internal chemical reaction, which occurs in the reaction chamber so that the volume of the reaction chamber increases and the volume of the fluid chamber decreases. Also disclosed is an injection device in which the piston moves in response to the pressure applied.

In various embodiments, the invention is intended to include all combinations and variations of the various functions described herein. For example, the formulations described herein can be used in any of the devices as will be appreciated by those skilled in the art reading these descriptions. Similarly, for any of the devices described herein, there is a corresponding method of using a viscous fluid, typically a device for delivering a drug. The present invention also includes a method of making an apparatus that includes assembly of components. The present invention further includes a kit containing separate chemical institution components as well as chemical institutions and other components assembled into a syringe. The present invention may be further characterized by measurements described herein, such as output density properties or any other measured properties described in the figures, examples or elsewhere. For example, it is characterized by an upper or lower limit or a range determined by the measurements described herein.

Various aspects of the invention are described using the term "comprising", but in more limited embodiments, the invention instead "becomes essential" or more narrowly "from". Can be described using the word "consisting of".

In any of the chemical institutions, CO is typically activated directly or indirectly to initiate gas generation within the chemical institution, eg, acid and bicarbonate are mixed and reacted in solution.
There may be a start plunger to generate ₂ . Preferably, the chemical engine locks the initiator plunger in place so that the reaction chamber remains closed to the atmosphere and no pressure is lost other than moving the plunger to push the fluid out of the fluid compartment. It has a function to perform (lag, etc.).

In various aspects, the invention is a method of making a formulation, syringe, formulation or syringe, typically comprising a syringe body, an inflatable compartment, a plunger (eg, a piston) and a viscous fluid component that is preferably a drug. Can be defined as. Typically, of course, the needle is connected to the drug compartment. In some embodiments, the expansion compartment may be releasably attached so that the expansion compartment portion (also referred to as the reaction chamber) can be separated from the chemical compartment. In some embodiments, the invention presents a formulation (s) and / or released gas (typically CO ₂ ) in addition to a method of pushing a solution through a syringe or a method of administering a drug or instrument. )
Can be defined as a system containing. The drug is a conventional drug or, in a preferred embodiment,
It may be a biological product (s) such as a protein. Any aspect of the invention may be characterized by a single function or any combination of functions described anywhere in this description.

A preferred embodiment of the present invention is
-Delivery of viscous fluids (eg, greater than 20 cP) with a flow velocity of 0.06 mL / sec or higher-Demand-based energy that excludes the need to store energy-Minimum starting force to prevent syringe breakage-Throughout the injection event Provided is a chemical institution capable of providing a relatively constant pressure / fluid viscosity to prevent stall or an adjustable pressure or pressure profile depending on the user's requirements. The present invention provides a gassing chemical reaction to generate demand-type pressure that can be used for delivery of pharmaceutical formulations by parenteral delivery. Pressure can be generated by mixing two reactive materials that generate gas. The advantage of this gas generation reaction over the prior art is that it provides rapid delivery (less than 20 seconds) of fluids with viscosities greater than 20 cP and provides a substantially flat pressure vs. time profile as shown in the examples. It can be done in a way that minimizes the required mounting space while maintaining. A further advantage of the present invention is that the pressure vs. time profile can be modified for different fluids, non-Newtonian fluids, patient requirements or devices.

The following is a brief description of the drawings, which are shown for purposes of illustrating exemplary embodiments disclosed herein, and are not intended to limit them.

It is a figure of the chemical reaction which produces the gas for moving a piston in a room. FIG. 5 is a diagram of a first embodiment of an apparatus for delivering a fluid by a chemical reaction. Here, the chemical reaction occurs when two kinds of dry chemical reagents are dissolved in a solvent and react. This figure shows a storage device in which the desiccant is separated from the solvent. It is a figure which shows the apparatus of FIG. 2 after the drying reagent was mixed with a solvent. It is a figure which shows the device of FIG. 2 which has a piston pushed by a gas pressure to deliver a fluid. FIG. 5 illustrates another exemplary embodiment of an apparatus for delivering a fluid by a chemical reaction of two reagents in a solvent. The device is made up of four separate parts that are coupled to form a coupling device similar to the device shown in FIG. FIG. 5 is a diagram of a first embodiment of an apparatus for delivering a fluid by a chemical reaction. Here, the chemical reaction occurs when the chemical reagent is exposed to heat. The device includes a heat source. FIG. 5 is a cross-sectional view of a first exemplary embodiment of an injection device. The present embodiment uses a one-way valve to create two separate chambers. FIG. 6 is a cross-sectional perspective view of an engine according to an exemplary embodiment of FIG. FIG. 5 is a cross-sectional view of a second exemplary embodiment of an injection device. The present embodiment uses a seal to create two separate chambers and a ring of teeth to break the seal. 9 is a cross-sectional perspective view of the engine according to the second exemplary embodiment of FIG. FIG. 5 is a cross-sectional view of a third exemplary embodiment of an injection device. In this embodiment, the upward traction of the handle (ie, away from the barrel of the device) breaks the seal between the two separate chambers. This figure shows the device prior to the upward traction of the handle. FIG. 5 is a cross-sectional perspective view of the engine in the third exemplary embodiment of FIG. 11 prior to the upward traction of the handle. FIG. 3 is a cross-sectional perspective view of the engine according to the third exemplary embodiment of FIG. 11 after the handle has been pulled upward. FIG. 5 is a profile of an exemplary embodiment showing an institution that uses encapsulated reagents. This figure shows a device in a stored state. FIG. 5 is a profile of an exemplary embodiment showing an institution that uses encapsulated reagents. This figure shows the device in use. FIG. 5 is a perspective view of a first exemplary embodiment of a patch pump that injects fluid using a chemical reaction. Here, the engine and the fluid chambers are adjacent and both have hard sidewalls. FIG. 5 is a perspective view of a second exemplary embodiment of a patch pump that injects fluid using a chemical reaction. Here, the engine is at the top of the fluid chamber, both with flexible walls. The engine expands and pushes the fluid chamber. This figure shows a patch pump when the fluid chamber is empty and before use. It is a perspective view of the patch pump of FIG. 17 when the fluid chamber is full. FIG. 5 is a profile of another exemplary embodiment of a syringe that uses a gassing chemical reaction. Here, the stopper is urged by the compression spring to proceed through the reagent chamber, and its contents are surely poured into the reaction chamber. It is a bottom view which shows the inside of the push button member in the syringe of FIG. It is a top view of the stopper used in the syringe of FIG. FIG. 5 is a graph showing a pressure vs. time profile for delivery of silicone oil when different amounts of water are injected into the reaction chamber. The y-axis is the gauge pressure (Pa) and the x-axis is the time (seconds). The plot shows the results for conditions where three different amounts of water, -0.1 mL, 0.25 mL and 0.5 mL were used. It is a graph which shows the volume vs. time profile for the delivery of 73cP silicone oil when the release agent (NaCl) is added to the reaction chamber. The y-axis is volume (ml) and the x-axis is time (seconds). A volume-to-time graph for delivery of a 73cP silicone fluid showing the use of a modified or mixed bicarbonate morphology, the reaction chamber remains 100% received, 100% lyophilized, 75% received / 25. Includes% lyophilization or 50% as received / 50% lyophilization. A pressure vs. time graph for delivery of a 73 cP silicone fluid showing the use of a modified or mixed bicarbonate morphology, the reaction chamber remains 100% received, 100% lyophilized, 75% received / 25. Includes% lyophilization or 50% as received / 50% lyophilization. It is a normalized pressure vs. time graph of delivery of 73cP silicone fluid in the initial period. The use of modifications or mixtures of bicarbonate morphology has been demonstrated and the reaction chamber is 100% lyophilized, 100% lyophilized, 75% lyophilized / 25% lyophilized or 50% lyophilized / 50% lyophilized. Including drying. It is a normalized pressure vs. time graph of the delivery of 73cP silicone fluid in the second period. The reaction chamber contains bicarbonates of different or mixed morphologies, 100% lyophilized, 100% lyophilized, 75% lyophilized / 25% lyophilized and 50% lyophilized / 50% lyophilized. there were. FIG. 5 is a volume vs. time graph for delivery of a 73cP silicone fluid showing the use of reagents with different dissolution rates or structures. The institution received 100% baking soda and citric acid powder, 100% Alka-Seltzer adjusted to a similar chemical ratio, 75% As-received powder / 25% Alka-Seltzer, 50%, 25% received. Included either as-is powder / 75% Alka-Seltzer. FIG. 5 is a volume vs. time graph for delivery of a 73cP silicone fluid showing the use of reagents with different dissolution rates or structures. The institution received 100% baking soda and citric acid powder, 100% Alka-Seltzer adjusted to a similar chemical ratio, 75% As-received powder / 25% Alka-Seltzer, 50%, 25% received. Included either as-is powder / 75% Alka-Seltzer. FIG. 5 is a pressure vs. time graph for delivery of a 1 cP aqueous fluid showing the use of reagents with different dissolution rates or structures. The institution received 100% baking soda and citric acid powder, 100% Alka-Seltzer adjusted to a similar chemical ratio, 75% As-received powder / 25% Alka-Seltzer, 50%, 25% received. Included either as-is powder / 75% Alka-Seltzer. FIG. 5 is a normalized pressure vs. time graph for delivery of a 73cP silicone fluid showing the use of reagents with different dissolution rates or structures. The institution received 100% baking soda and citric acid powder, 100% Alka-Seltzer adjusted to a similar chemical ratio, 75% As-received powder / 25% Alka-Seltzer, 50%, 25% received. Included either as-is powder / 75% Alka-Seltzer. The pressures are normalized by normalizing the curves in FIG. 29 to their maximum pressure. FIG. 31 is a normalized pressure vs. time graph magnifying the first 3 seconds of FIG. FIG. 5 is a volume vs. time graph for delivery of a 73 cP silicone fluid in which the reaction chamber contains either sodium bicarbonate (BS), potassium bicarbonate or a 50/50 mixture. FIG. 3 is a pressure vs. time graph of a third set of tests in which the reaction chamber is delivery of a 73 cP silicone fluid containing either sodium bicarbonate (BS), potassium bicarbonate or a 50/50 mixture. 3 is a kinetics graph of a third set of tests in which the reaction chamber is the delivery of a 73 cP silicone fluid containing either sodium bicarbonate (BS), potassium bicarbonate or a 50/50 mixture. 4 is a volume vs. time graph of the fourth set of tests for silicone oils. Illustrates a conduit with an opening that can be used to deliver a solution into a reaction chamber. Shown is a measured pressure vs. time profile for a chemical institution using mixed sodium bicarbonate and potassium bicarbonate delivering silicone oil through 19 mm long and 27 gauge thin wall needles. Volume vs. delivery time for controls (without NaCl) and systems using solid NaCl as a nucleating agent (NaCl). The force vs. time profiles from two different chemical institutions delivering 1 mL of 50 cP fluid through a 27 gauge thin wall needle (1.9 cm in length) are shown. The force vs. time profiles from two different chemical institutions (formulations 3 and 4) delivering 3 mL of 50 cP fluid through a 27 gauge thin wall needle (1.9 cm in length) are shown. The force vs. time profile from a chemical institution (formulation 5) delivering 3 mL of 50 cP fluid through a 27 gauge thin wall needle (1.9 cm in length) is shown. The pressure profile at the constants for the compositions described on the right side of the figure is shown. The observed pressure increased in the order of control <nucleation surface << expandel particles <oxalic acid <diatomaceous earth <calcium oxalate. It shows the similarity of the effects of vibration and added diatomaceous earth in enhancing gas generation. Illustrates the displacement of a viscous fluid powered by a chemical institution containing 5, 10 or 50 mg of diatomaceous earth acting as potassium bicarbonate, citric acid and convection agent. An instrument for measuring the power density of a chemical institution is schematically illustrated.

Glossary Chemical Institutions-Chemical institutions generate gas through chemical reactions, and the generated gas is used to power another process. Typically, the reaction is not combustion, and in many preferred embodiments the chemical institution is of CO ₂ from the reaction of a carbonate (typically sodium carbonate or preferably potassium carbonate) with an acid, preferably citric acid. Powered by the outbreak.

In the context of chemical institutions, closed vessels prevent the gas from leaking into the atmosphere so that the force of the generated gas can be applied to the plunger. In the assembled device (typically a syringe), the plunger is driven by the generated gas to push the fluid out of the fluid compartment. In many embodiments, the container is occluded at one end by a one-way valve.
Surrounded by the walls of the chamber in a direction orthogonal to the central axis and blocked at the other end by a movable plunger.

Viscosity can be defined in two ways: "kinematic viscosity" or "absolute viscosity". Kinematic viscosity is a measure of the reactive flow of a fluid under applied force. The SI unit of kinematic viscosity is mm ² / sec, which is 1 centimeter stalk (cSt). Absolute viscosity, sometimes called dynamic viscosity or simple viscosity, is the product of kinematic viscosity and fluid density. The SI unit of absolute viscosity is millipascal seconds (mPa seconds) or centipores (cP), where 1 cP = 1 mPa seconds. Unless otherwise specified, the term viscosity always refers to absolute viscosity. Absolute viscosity, capillary rheometer, cone and plate rheometer (cone and p)
It may be measured by late rheometer) or any other known method.

The fluid may be either Newtonian or non-Newtonian. Non-Newtonian fluids should be characterized at different shear rates, including those similar to the injection shear rate. In this case, the viscosity of the fluid may be approximated using the Hagen-Poiseuille equation when a known force is used for injection through a known needle diameter and length at a known fluid velocity. The present invention is suitable for both Newtonian and non-Newtonian fluids.

Plungers (also called "expansion plungers") are CO ₂ generated in chemical institutions.
Any component that moves or deforms in response to, which can directly or indirectly transmit force to a liquid in a compartment adjacent to or indirectly connected to a chemical institution. For example, the plunger pushes the piston, which in turn can push the liquid in the syringe. There are numerous types of plungers described in this application and the prior art, and the formulations and designs of the present invention are generally applicable to a large number of plunger types.

The initiation plunger is a mobile component usually used to initiate a reaction by directly or indirectly inducing a mixture of acid, carbonate and water. Preferably, the starting plunger is locked in place to prevent any loss of pressure and thus direct all generated pressure to the fluid ejected from the fluid chamber.

The term "parenteral" refers to a means of delivery that does not pass through the gastrointestinal tract, such as injection or infusion.

The pressure vs. time profile may include a burst, where the burst is described as a second increase in the profile of pressure during delivery.

The process of the present disclosure may be used with both manual syringes and automatic syringes and is not limited to cylindrical shapes. The term "syringe" is used interchangeably to refer to manual syringes and automatic syringes of any size and shape. The term "injection device" is used to refer to any device that can be used to inject a fluid into a patient, including, for example, syringes and patch pumps. In a preferred embodiment, any of the chemical institutions described herein may be part of a syringe and the invention includes these syringes.

FIG. 1 illustrates the generation of pressure by a chemical reaction for use in the delivery of a pharmaceutical formulation by injection or infusion. With reference to the left side of the figure, one or more chemical reagents 100 are encapsulated in the reaction chamber 110. One side of the chamber may move in relation to the other side of the chamber and acts as a piston 120. The chamber 110 has a first volume prior to the chemical reaction.

The chemical reaction is then initiated in the room, as indicated by the "RXN" arrow. The gaseous by-product 130 is generated at the same rate, n (t) (in the formula, n is the mole of the generated gas and t is the time). The pressure is proportional to the amount of gaseous by-products 130 produced by the chemical reaction, as seen in formula (1).
P {t)-[n {t) · T] IV (1)
In formula (1), T represents temperature and V represents the volume of chamber 110.

The volume of the chamber 110 remains fixed until the additional force generated by the gas pressure on the piston 120 exceeds the force required to push the fluid through the needle of the syringe. The force required depends on the mechanical components present in the system, such as the frictional force and the mechanical advantages provided by the structure of the coupler, the syringe needle diameter and the viscosity of the fluid.

Once the minimum pressure required to move the piston 120 is exceeded, the volume of the reaction chamber 110 begins to increase. The operation of piston 120 initiates delivery of fluid within the syringe.
The pressure in the chamber 110 depends on both the rate of reaction and the rate of volume expansion, as represented by equation (1). Preferably, sufficient gas is generated to occupy the volume expansion without generating excessive excess pressure. This can be achieved by adjusting the rate of reaction and outgassing in chamber 110.

The pressure rise from the gaseous by-product 130 produced by the chemical reaction can be used to directly push the fluid adjacent to the piston 120 through the syringe. Pressure rise is an indirect method,
The fluid can also be pushed, for example, by establishing a mechanical contact between the piston 120 and the fluid by a rod or shaft connecting the piston 120 to the stopper of a prefilled syringe containing the fluid.

One or more chemical reagents 100 are selected so that the reaction produces a gaseous by-product 130. Suitable chemical reagents 100 include reagents that react to produce gaseous by-products 130. For example, citric acid (C ₆ H ₈ O ₇ ) or acetic acid (C ₂ H ₄ O ₂ ) will react with sodium bicarbonate (NaHCO ₃ ) to generate carbon dioxide, CO ₂ .
This can be initiated when the two reagents are dissolved in a common solvent such as water. Alternatively, a single reagent can generate gas when triggered by an initiation factor such as light, heat or dissolution. For example, a single reagent 2,2'-azobisisobutyronitrile (AIBN) can be used from 50 ° C.
It can be decomposed at a temperature of 65 ° C. to generate nitrogen gas (N ₂ ). Chemical reagents (s)
Is selected so that the chemical reaction can be easily controlled.

One aspect of the present disclosure provides (i) sufficient force to deliver a viscous fluid in a short time, eg, less than 20 seconds, and (ii) a small package suitable for driving the syringe. It is a combination of various components. In order to achieve the desired injection, the time, size and information must all be aligned at the same time. The package size for a chemical institution is determined by the volume of reagents, including solvent, which is measured in standard conditions (25 C, 1 atm) after all components are mixed and CO ₂ is released.

The molar concentration of CO ₂ vs. H ₂ CO ₃ is given by pH. The pKa of H ₂ CO ₃ is 4
.. 45. For pH well below this value, the ratio of CO2 to H2CO3 is approximately 100%. For pH close to pKa (eg 4.5 to 6.5), the value will decrease from 90% to 30%. For pH greater than 7, the system is approximately H ₂ C
It consists of O ₃ and will not have CO ₂ . Suitable acids should therefore provide a buffer for the system to maintain a pH below 4.5 from the beginning to the end of the duration of the injection event. The chemical reaction is an injection event within the time frame of the injection event (eg, within 5 seconds or within 10 seconds or 2).
It is not necessary to reach 100% conversion within 0 seconds), but in general the conversion should approach at least 30-50% to minimize the generation of excess pressure (conversion reacted). Defined as the molar percentage of acid, in some embodiments in the range of 30-80%, in some embodiments in the range of 30-50%). In some embodiments, the conversion of the CO ₂ reactant (such as sodium bicarbonate or potassium bicarbonate) is at least 30%, preferably at least 50% or at least 70% and less than 95% in some embodiments. ..

Acids that are liquid at room temperature, such as glacial acetic acid (pKal 4.76) and butyric acid (pKa 4.82), are suitable. Preferred acids are organic acids that are solid at room temperature, and these acids have a slight odor and do not react with the device. In addition, they may be packaged as powders with different morphologies or structures to provide a means of controlling the rate of dissolution. Preferred acids include citric acid (pH: 2.1 to 7.2 (pKa: 3.1; 4.8; 6.4)) and oxalic acid (pH: 0.3 to 5.3 [pKa: 1. 3; 4.4]), tartaric acid (tartart)
ic acid) (pH: 2 to 4; [pKal = 2.95; pKa2 = 4.25]) and phthalic acid (pH: 1.9 to 6.4 [pKa: 2.9; 5.4]) included. HCl is added in the experiment. Surprisingly, it was found that reducing the pH to 3 did not accelerate the release of CO ₂ .

In some preferred embodiments, citric acid is used in systems in which the injection event occurs with a reaction conversion between 15 and 50%. It may be desirable to take advantage of the pressure generated by the rapid rise in CO ₂ and thus the low conversion. Due to the buffering behavior of this acid, the pH rises above 5.5, so the ratio of CO ₂ to H ₂ CO ₃ produced during the reaction will decrease at high conversions. This system will have less pressure rise in the final stages of the reaction after the completion of injection. In other situations, it may be desirable to utilize a complete response cycle to modify the response so that it is near completion at the end of the injection event. In some embodiments, tartaric acid and oxalic acid are preferred choices due to their low pKa values.

In some preferred embodiments, the bicarbonate is added as a saturated solution to a swelling compartment containing a solid acid or salt, a solid acid mixed with other components such as bicarbonate or other additives.
In other embodiments, water is added to the piston containing a solid acid mixed with bicarbonate and other components. In some other preferred embodiments, additional CO at the end of injection
_{2 An} aqueous bicarbonate solution is added to the solid composition containing the solid bicarbonate to provide the product. In yet other embodiments, the bicarbonate may be present as a moistened or only partially dissolved solid. Any form of bicarbonate may react with the dissolved acid. For example
In some preferred embodiments, the bicarbonate is mixed with a solution of citric acid.

If the chemistry remains in a small reaction volume, i.e., if a relatively large amount of reagent remains in a small volume of liquid (saturated solution) in a pressurized system, the process of producing CO ₂ (g) is significantly further. It gets complicated. Depending on the situation, the important speeds that limit the steps are here:
• Depending on the dissolution rate of the solid reagent, the effectiveness and diffusion rate of bicarbonate ions, the rate of CO ₂ withdrawal from the bicarbonate surface, and the need for a system for releasing CO ₂ (g) from the solution, the parameters are: It may be adjusted independently or consistently to minimize overshoot and maintain a flat pressure profile curve where the effects of volume expansion of the chemical reaction chamber do not reduce pressure and slow delivery.

The effectiveness of bicarbonate can be an important factor in achieving fast delivery of viscous fluids. In solution, the salt of bicarbonate is in equilibrium with the active species in the reaction, bicarbonate ion. Bicarbonate ions may be free species or strongly associated. Bicarbonate concentrations can be determined by adding ethaneol to reduce kinetics or by adding N-methylformamide or N-methylacetamide to increase kinetics, utilizing common ionic effects and saturation points. It can be controlled by changing the solvent polarity, such as by utilizing a relatively high content of bicarbonate in excess of. Bicarbonate is preferably 9 g in 100 mL
More preferably, it has a solubility in water greater than 25 g in 100 mL. In some preferred embodiments, a saturated solution of potassium bicarbonate is added to the piston containing the acid. In other embodiments, water is added to the piston containing solid acid and potassium bicarbonate.

The pressure profile during delivery may be changed by changing the rate of dissolution. For example, the addition of a saturated solution of potassium bicarbonate to a piston containing solid bicarbonate and solid bicarbonate is the first rapid outburst of CO ₂ and solids when the dissolved bicarbonate is reacting with the acid. It provides a second, secondarily maintained concentration of CO ₂ as the bicarbonate dissolves and becomes available. The rate of dissolution can be altered by varying the particle size or surface area of the powder, using bicarbonate or acid with several different species, encapsulation with a second component or varying solvent quality. By combining powders with different dissolution rates, the pressure vs. time profile may be altered to allow outbursts at constant pressure over time or pressure over time. The introduction of catalyst may be used for the same effect.

The pressure in the piston (reaction chamber) is determined by the concentration of CO ₂ released from the solution. Release may introduce a method of agitation or reduce the solubility of CO ₂ or its nucleation,
It can be facilitated by introducing a place that promotes growth and proliferation. The method of stirring may include the introduction of a rigid sphere suspended in the piston. Suitable spheres include hollow polymeric microspheres such as expand cell, polystyrene microspheres or polypropylene microspheres. When water or saturated bicarbonate is introduced into the piston, the external flow induces forces and torque on the sphere, resulting in their rotation with velocity w and initiating buoyancy-induced movement. The flow field generated by the rotation of the sphere improves gas diffusion towards the surface and promotes the elimination of CO ₂ from the liquid. The surface of the freely rotating sphere can also be modified by the active layer, such as by coating with bicarbonate. These spheres are initially heavy and unaffected by buoyancy. However, as the coating dissolves or reacts with the acid, the buoyancy will begin to move the sphere towards the surface of the liquid. During the aforementioned operation, the disproportionate force on the particles promotes spinning, reducing gas transfer rate-determining and increasing the elimination of CO ₂ from the liquid.

In some embodiments, salts, additives or other nucleating agents are added to facilitate the release of the dissolved gas into the empty volume. Examples of the nucleating agent include crystalline sodium chloride, calcium tartrate, calcium oxalate and sugar. Release can be facilitated by adding components that reduce the solubility of the gas. It can also be promoted by the addition of nucleating agents that promote the release of gas bubbles by nucleation, growth and heterogeneous nucleation.

In a preferred embodiment, the flow velocity vs. time is kept substantially constant so that the shear rates on the fluid are similar. For Newtonian fluids, the shear rate is proportional to the flow velocity and r ³
(In the formula, r is the radius of the needle). The change in shear rate can be defined as [(maximum flow rate-minimum flow rate) / minimum flow rate)] -100 when the flow starts after the first 2 or 3 seconds for a device in which the needle diameter does not change. In a preferred embodiment, the change in shear rate is less than 50%, more preferably less than 25%. The fluid may be Newtonian or non-Newtonian. 27 The typical flow rate in the delivery of a subcutaneous through a needle having a diameter in the range of 31 gauge from the gauge, the shear rate is from about 1x10 ⁴ 1x1
The non-Newtonian effect, which is 0 ⁴ s ^-1 , can be important, especially for proteins.

In some embodiments further described herein, an injection device using a gassing chemical reaction produces a fluid with a viscosity greater than 70 centipores (cP) that passes through a 27 gauge thin wall (TW) needle in less than 10 seconds. Used to displace. The 27 gauge thin wall needle has a nominal outer diameter of 0.
016 ± 0.0005 inches, nominal inner diameter 0.010 ± 0.001 inches and wall thickness 0.0
It has 03 inches. These results are expected to be obtained with needles with a larger nominal inner diameter.

The selection of chemical reagents (s) may be based on different factors. One factor is the dissolution rate of the reagent, that is, the rate at which the dry powder form of the reagent dissolves in a solvent such as water. The rate of dissolution can be altered by varying the particle size or surface area of the powder, encapsulating the powder with a coating that dissolves first, or by changing the solvent quality. Another factor is the desired pressure vs. time profile. The pressure vs. time profile can be controlled by changing the kinetics of the reaction. In the simplest case, the kinetics of a given reaction will depend on factors such as reagent concentration and temperature that depend on the "order" of the chemical reaction. 2
For many reagents 100, including those that must be mixed with seed drying reagents, the kinetics will depend on the rate of dissolution. For example, the pressure vs. time profile may be modified by mixing two powders with different dissolution rates to allow a profile with a constant pressure over time or a pressure outburst at a given time. The introduction of catalyst may be used for the same effect. Alternatively, the delivered volume vs. time profile may have a constant slope. The term "constant" refers to a given profile with a linear upward slope over a period of at least 2 seconds, with an acceptable deviation of ± 15% in the slope value.

This ability to regulate chemical reactions adapts the devices of the present disclosure to different fluids (having different volumes and / or viscosities), patient requirements or delivery device designs. Furthermore, the shape of the reaction chamber can affect the extent to which the accumulated pressure acts on the piston, while the chemical reaction proceeds independently of the outer shape of the reaction chamber.

The target pressure level for providing drug delivery can be determined by the mechanism of the syringe, the viscosity of the fluid, the diameter of the needle and the desired delivery time. The target pressure, along with the appropriate volume of the reaction chamber,
It is achieved by choosing the appropriate amount of reagent and stoichiometric ratio to determine n (molar of gas). The solubility of the gas in any liquid present in the reaction chamber that will not contribute to the pressure should also be considered.

If desired, a release agent may also be present in the reaction chamber to increase the rate of fluid delivery. If a solvent such as water is used to facilitate diffusion and intermolecular reactions, the resulting gas will have some solubility or stability in the solvent. The release agent promotes the release of any dissolved gas into the headspace of the chamber. The release agent reduces the solubility of the gas in the solvent. Exemplary release agents include nucleating agents that promote the release of gas bubbles by nucleation, growth and heterogeneous nucleation. An exemplary release agent is sodium chloride (NaCl). The presence of the release agent is often the rate that limits the factors of pressure generation for the drying (powder) reagent, which can increase the overall rate of many chemical reactions by increasing the rate of dissolution. .. The release agent can also be considered a catalyst.

In some preferred embodiments, the volume of the reaction chamber is 1 to 1.4 cm ³ or less, in some preferred embodiments 1 cm ³ or less, and in some embodiments 0.5 to 1 or 1.4 cm.
It is in the range of ³ . Other components of the device may be sized to fit the volume of the reaction chamber. A reaction chamber of 1 to 1.4 cm ³ or less allows the chemical reaction delivery of highly viscous fluids in a limited injection space or occupied area.

FIG. 2 illustrates one exemplary embodiment of an apparatus (here, a syringe) that can be used to deliver a viscous fluid that uses a chemical reaction between reagents to generate a gas. Syringe 400 is depicted here in a stored or unpressed state where the chemical reaction has not yet begun. Needles are not included in this figure. The syringe 400 includes a barrel 410 formed from the side wall 412 and whose interior space is divided into three separate chambers. The syringe is the top 40 of the barrel.
Starting with 2, it includes a reagent chamber 420, a reaction chamber 430 and a fluid chamber 440. Plunger 470
Is inserted into the upper end 422 of the reagent chamber. The one-way valve 450 exists at the lower end 424 of the reagent chamber and forms a radial surface. The one-way valve 450 is also present at the upper end 432 of the reaction chamber. The one-way valve 450 is directed to allow the material to leave the reagent chamber 420 and enter the reaction chamber 430. The lower end 434 of the reaction chamber is formed by the piston 460. Finally, the piston 460 is located at the upper end 442 of the fluid chamber. Barrel Orifice 416
Is at the lower end 444 of the fluid chamber and at the bottom end 404 of the syringe. Note that the one-way valve 450 is fixed in place and cannot move within the barrel 410. In contrast, the piston 460 can move within the barrel in response to pressure. In other words, the reaction chamber 430
It is defined by a one-way valve 450, a barrel side wall 412 and a piston 460.

The reaction chamber 430 may also be described as having a first end and a second end. The movable piston 460 is at the first end 434 of the reaction chamber, while the one-way valve 450 is at the second end 432 of the reaction chamber. In this figure, the reaction chamber 430 is directly on one side of the piston 460 and the fluid chamber 440 is directly on the other side of the piston.

The reagent chamber 420 contains at least one chemical reagent, solvent and / or mold release agent. Reaction chamber 430 contains at least one chemical reagent, solvent and / or release agent. Fluid chamber 44
0 includes the fluid to be delivered. As depicted herein, reagent chamber 420 contains solvent 480, reaction chamber 430 contains two different chemical reagents 482, 484 in the form of dry powder, and fluid chamber 440 contains high viscosity fluid 486. Again, please note that this figure is not drawn to scale. The chemical reagents do not fill the entire volume of the reaction chamber, as exemplified herein.
Instead, headspace 436 is present in the reaction chamber.

In a particular embodiment, the reagent chamber contains bicarbonate pre-dissolved in a solvent and the reaction chamber contains a dry acid powder. It turns out that passive mixing of reagents in the solvent was a problem that would reduce the speed of the reaction. Bicarbonate was pre-dissolved, but otherwise it was too slow to dissolve and participated in the gassing reaction. In a more specific embodiment, potassium bicarbonate was used. Sodium bicarbonate was found not to react rapidly. The citrate was used as a dry acid powder because it dissolved quickly and reacted quickly. Sodium chloride (NaCl) was included as a dry release agent along with citrate. Sodium chloride provided a nucleation site to release gas from the solution more rapidly.

Each chamber has a volume in which what is depicted in the figure is proportional to the height of the chamber. The reagent chamber 420 has a height of 425, the reaction chamber 430 has a height of 435, and the fluid chamber 440 has a height of 4.
Has 45. In this unpressed state, the volume of the reaction chamber is sufficient to contain the solvent and the two chemical reagents.

In certain embodiments, the volume of the reaction chamber is 1 cm ³ or less. Other components of the device may be sized to fit the volume of the reaction chamber. A reaction chamber of 1 cm ³ or less allows the chemical reaction delivery of highly viscous fluids in a limited injection space or occupied area.

In FIG. 3, the plunger 470 is pressed, i.e. the syringe is in the pressed state. This operation opens the one-way valve 450 and allows the solvent 480 to enter the reaction chamber 430, 2
Dissolve the seed chemical reagents (here exemplified as bubbles in a solvent). Plunger 47
After 0 is pressed, the one-way valve 450 closes in a state where no further pressure is applied to the one-way valve (this figure shows the valve in the open state). In certain embodiments, the barrel sidewall 412 may include a groove 414 at the lower end 424 of the reagent chamber, or the plunger 47.
It is molded to capture zeros. In other words, the plunger 470, after being pressed, cooperates with the lower end 424 of the reagent chamber 420 to lock the plunger in place.

In FIG. 4, the dissolution of the two chemical reagents in the solvent is the gas 4 as a by-product of the chemical reaction.
It resulted in 88 outbreaks. As the amount of gas increases, the pressure exerted on the piston 460 increases until a threshold is reached, after which the piston 460 moves downward towards the bottom end 404 of the syringe (as indicated by the arrow). This increases the volume of the reaction chamber 430 and decreases the volume of the fluid chamber 440. As a result, the high-viscosity fluid 486 in the fluid chamber is distributed through the orifice. In other words, the combined volume of the reaction chamber 430 and the fluid chamber will remain constant, but the volume ratio of the reaction chamber to the fluid chamber 440 will increase as gas is generated in the reaction chamber. It should be noted that the one-way valve 450 does not allow the gas 488 to leak from the reaction chamber to the reagent chamber.

The syringe has the following elements: (i) particle size of dry powder reagent, (ii) solubility of reagent, (ii)
i) The mass of the reagent and the amount of mold release agent and (iv) the shape composition of the chamber for consistent filling and packaging can provide consistent force if properly controlled.

FIG. 5 illustrates another variant of the apparatus 700 that uses chemical reactions between reagents to generate gas. This figure is in a stored state. The barrel in FIG. 2 is shown as being made from an integral side wall, whereas the barrel in the device of FIG. 5 is made of several shorter pieces. This structure can simplify the manufacture and filling of various chambers of the overall device. Another major difference in this variant is that the piston 760 is composed of three different parts: a push surface 762, a rod 764 and a stopper 766, as further described herein.

The reagent chamber 720 is made from a first portion 726 that starts at the top of FIG. 5 and has a first side wall 728 that defines the sides of the reagent chamber. The plunger 770 is inserted into the upper end 722 of this portion to seal the end. The first portion 720 then circulates the reagent chamber 720 with solvent 780.
May be turned upside down to fill with.

The second portion 756, including the one-way valve 750, may then be connected to the lower end 724 of the first portion to seal the reagent chamber 720. The second side wall 758 surrounds the one-way valve. The lower end 724 of the first portion and the upper end 752 of the second portion may be connected using a known means such as a thread (eg, luer lock). As illustrated herein, the lower end of the first portion will have a female screw, while the upper end of the second portion will have a male screw.

The third portion 736 is used to form the reaction chamber 730 and is also formed from the third side wall 738. The push surface 762 of the piston is located inside the third side wall 738. After placing the chemical reagent, solvent and / or mold release agent on the pressing surface, the lower end 754 of the second portion and the upper end 732 of the third portion are connected. The two reagents 782 and 784 are depicted here. The rod 764 of the piston extends downward from the push surface 762.

Finally, the fourth portion 746 is used to form the fluid chamber 740. This fourth portion is formed from a fourth side wall 748 and a conical wall 749 forming a tapered orifice 716 through which fluid will be released. The orifice is the lower end 7 of the fluid chamber.
Located at 44. The fluid chamber may be filled with the fluid to be delivered, at which time the stopper 7
66 may be placed in the fluid chamber. As can be seen here, the stopper 766 may include a vent 767 so that air leaks out of the fluid chamber when the stopper is pushed down to the surface of the fluid 786 to prevent air from being trapped in the fluid chamber. The cap 768 attached to the lower end of the piston rod 764 may be used to cover the vent hole 767. Alternatively, the lower end of the piston rod may be inserted into the ventilation hole. Next, the lower end portion 734 of the third portion and the upper end portion 742 of the fourth portion are connected.

As described above, the piston 760 in this modified form has a push surface 762 that is joined together.
, Formed from rod 764 and stopper 766. The empty volume 790 therefore resides between the reaction chamber 730 and the fluid chamber 740. The size of this empty volume may vary as needed. For example, it may be useful to make the overall device longer so that it can be more easily gripped by the user. Otherwise, this variant operates in the same manner as described above with respect to FIGS. The push surface portion of the piston acts in the reaction chamber, and the stopper portion of the piston acts in the fluid chamber. It should also be noted that the push surface, rod, stopper and optional cap may be one integral part or a separate part.

FIG. 6 illustrates an exemplary embodiment of a device (again, a syringe) that can be used to deliver a viscous fluid using a heat-initiated chemical reaction to generate a gas. Again, the syringe 800 is depicted here in storage.

The barrel 810 is formed from the side wall 812 and the interior space is two separate chambers, the reaction chamber 8
It is divided into 30 and a fluid chamber 840. The reaction chamber 830 is located at the upper end 802 of the syringe. The upper end 832 of the reaction chamber is formed by a radial wall 838. The heat source 850 that may be used for heating is located in the reaction chamber. The heat source 850 may be located on the radial wall 838 or, as depicted herein, on the barrel sidewall 812.

The lower end 834 of the reaction chamber is formed by the piston 860. The reaction chamber 830 is defined by a radial wall 838, a barrel side wall 812 and a piston 860. The piston 860 is also present at the upper end 842 of the fluid chamber. The orifice 816 of the barrel is located at the lower end 844 of the fluid chamber, i.e. the lower end 804 of the syringe. Again, the reaction chamber piston 860
Only portions can move within barrel 810 in response to pressure. The radial wall 838 is fixed in place and dense to prevent gas from passing through.

The reaction chamber contains the chemical reagent 882. For example, the chemical reagent may be 2,2'-azobisisobutyronitrile. Headspace 836 may be present in the reaction chamber. Fluid chamber 8
40 includes fluid 886.

The activation trigger 852 may be present on the syringe and may be, for example, on the outer surface 816 of the upper end near the finger flange 815 or the barrel sidewall. When activated, the heat source 850 generates heat. The heat source may be, for example, an infrared light emitting diode (LED). The chemical reagent 882 is
It is sensitive to heat and produces gas (here N2). The pressure generated by the gas moves the piston 860 to release the highly viscous fluid 886 in the fluid chamber 840.

It should be noted again that the piston may be of the push surface, rod and stopper type shown in FIG. 5 instead. This type can be appropriate here as well.

In another embodiment, it of the device can be used to deliver a viscous fluid using a chemical reaction initiated by light to generate a gas. This embodiment is substantially identical to the type described in FIG. 6, except that the heat source is here replaced by a light source 850 that can shed light on the reaction chamber 830. The chemical reagent 884 is here sensitive to light and produces gas when exposed to light. For example, the chemical reagent may be silver chloride (AgCl). The pressure generated by the gas moves the piston and releases a highly viscous fluid in the fluid chamber. Figure 5
The piston type of is also used here as needed.

Any suitable chemical reagent or reagent may be used to generate the gas. For example, bicarbonate will react with an acid to form carbon dioxide. Sodium bicarbonate, potassium bicarbonate and ammonium bicarbonate are examples of suitable bicarbonates. Suitable acids may include acetic acid, citric acid, potassium bitartrate, disodium pyrophosphate or calcium dihydrogen phosphate. Any gas such as carbon dioxide, nitrogen gas, oxygen gas, and chlorine gas may be generated by a chemical reaction. Desirably, the gas generated is inert and nonflammable. Metallic carbonates such as copper carbonate or calcium carbonate may be thermally decomposed to produce CO ₂ and the corresponding metal oxides. As another example, 2,2'-azobisisobutyronitrile (AIBN) may be heated to generate nitrogen gas. In yet another example, the reaction of certain enzymes (eg yeast) with sugar produces CO ₂ . Some substances easily sublimate from solids to gases. These materials include, but are not limited to, naphthalene and iodine. Hydrogen peroxide can be decomposed by an enzyme (eg, catalase) or a catalyst such as manganese dioxide to generate oxygen gas.

It is conceivable that the highly viscous fluid distributed using the apparatus of the present disclosure may be a solution, dispersion, suspension, emulsion or the like. High viscosity formulations may contain proteins such as monoclonal antibodies or some other proteins that are therapeutically useful. Protein is about 15
It may have a concentration of 0 mg / ml to about 500 mg / ml. High viscosity fluids may have an absolute viscosity of about 5 centipoise to about 1000 cmpoise. In other embodiments, the viscous fluid has an absolute viscosity of at least 40 centipores or at least 60 centipores. The high viscosity fluid may further contain a solvent or non-solvent such as water, a perfluoroalkane solvent, safflower oil or benzyl benzoate.

7 and 8 are different views of a first exemplary embodiment of an injection device (here a syringe) that can be used to deliver a viscous fluid that uses a chemical reaction between reagents to generate a gas. Is. Syringe 300 is depicted here in a stored or unpressed state where the chemical reaction has not yet begun. FIG. 7 is a sectional view of the syringe engine, and FIG. 8 is a perspective view.

The syringe 300 includes a barrel 310 whose internal space is divided into three separate chambers.

The syringe begins at the top 302 of the barrel, with the upper chamber 320, lower chamber 330 and fluid chamber 3
Includes 40. These three chambers are coaxial and are here depicted as having a cylindrical shape. The lower chamber can also be considered as a reaction chamber.

The plunger 370 is inserted into the upper end 322 of the upper chamber, and the stopper 372 of the plunger advances only through the upper chamber. The one-way valve 350 exists at the lower end 324 of the upper chamber and forms a radial surface. The one-way valve 350 is also present at the upper end 332 of the lower chamber. One-way valve 350
Is directed to allow material to leave the upper chamber 320 and enter the lower chamber 330. The piston 360 is located at the lower end 334 of the lower chamber. The piston 360 is the upper end 34 of the fluid chamber.
It also exists in 2. As illustrated herein, the piston is formed from at least two parts, a push surface 362 at the lower end of the lower chamber and a head 366 at the upper end of the fluid chamber. The needle 305 is located at the lower end 344 of the fluid chamber and at the bottom end 304 of the syringe.
Note that the one-way valve 350 is fixed in place and cannot move within the barrel 310, or in other words, does not move relative to the barrel. In contrast, the piston 360 can move within the barrel in response to pressure. In other words, the lower chamber 330 is defined by a one-way valve 350, a continuous side wall 312 of the barrel and a piston 360.

The lower chamber 330 may also be described as having a first end and a second end. The movable piston 360 is at the first end 334 of the lower chamber, while the one-way valve 350 is the second of the lower chamber.
At the end of 332. In this figure, the lower chamber 330 is directly above one side of the piston 360 and the fluid chamber 340 is directly above the other side of the piston.

As mentioned above, the piston 360 is formed from at least the push surface 362 and the head 366. These two parts may be physically connected, for example, by a rod (not shown) having a push surface and a head on opposite ends. Alternatively, it is conceivable that the incompressible gas may be located between the push surface and the head. The empty volume 307 is therefore the lower chamber 330
Will exist between and the fluid chamber 340. The size of this empty volume can vary as needed. For example, it may be useful to make the overall device longer so that it can be easily grasped by the user. Alternatively, as further illustrated in another embodiment of FIGS. 9 and 10 herein, the piston may use a balloon that acts as a push surface and acts on the head 366. In yet another variant, the piston may be a single portion, with the push surface on one side of the single portion and the head on the opposite side of the single portion.

Upper chamber 320 contains at least one chemical reagent or solvent. The lower chamber 330 contains at least one chemical reagent or solvent. The fluid chamber 340 contains the fluid to be delivered. It is generally considered that the drying reagents will be placed in the lower chamber and the wet reagents (ie, solvent) will be placed in the upper chamber. As depicted herein, the upper chamber 320 will contain a solvent, the lower chamber 330 will contain two different chemical reagents in dry powder form, and the fluid chamber 340 will contain a viscous fluid. Reagents (s) in any of the chambers may be encapsulated for easier handling during manufacture. Each chamber has a volume in which what is depicted in the figure is proportional to the height of the chamber. In this unpressed state, the volume of the lower chamber is sufficient to contain the solvent and the two chemical reagents.

When the plunger in the syringe of FIGS. 7 and 8 is pressed, additional pressure is applied to the one-way valve 3
50 is opened and the solvent in the upper chamber 320 enters the lower chamber 330 to dissolve the two chemical reagents.
After the plunger 370 is sufficiently pressed, the one-way valve 350 closes with no further pressure applied to the one-way valve. As illustrated here, the plunger is a thumb rest 37.
Includes pressure lock 378 on shaft 374 close to 6 and thumb rest. The pressure lock works with the upper surface 326 of the upper chamber to lock the plunger in place. The two chemical reagents are
They may react with each other in a solvent to generate gas in the lower chamber. As the amount of gas increases, the pressure on the push surface 362 of the piston 360 increases until it reaches a threshold, after which the piston 360 moves downward toward the bottom end 304 of the syringe. This increases the volume of the lower chamber 330 and decreases the volume of the fluid chamber 340. This causes the highly viscous fluid in the fluid chamber to be distributed (by the head 366) through the orifice. In other words,
The combined volume of the lower chamber 330 and the fluid chamber will remain constant, but the volume ratio of the lower chamber to the fluid chamber 340 will increase as gas is generated in the reaction chamber. One-way valve 3 to keep in mind
Fifty is to prevent gas from leaking from the lower chamber to the upper chamber. Similarly, the pressure lock 378 on the plunger causes the stopper 372 to act as a secondary aid to the one-way valve 350.
It also prevents the plunger from being pushed up and pushed out of the upper chamber.

In some embodiments, the upper chamber contains bicarbonate pre-dissolved in a solvent and the lower chamber contains a dry acid powder. Passive mixing of reagents in the solvent, ie mixing both dry powders into the reaction chamber and adding water, reduces the speed of the reaction. One reagent may be pre-dissolved. For example, bicarbonate may be pre-dissolved. In a more specific embodiment, potassium bicarbonate is recommended. Sodium bicarbonate does not react rapidly and therefore C
O ₂ production and injection rate are slower. Citric acid is a preferred dry acid powder because it is not only safe, but also dissolves well and reacts quickly. Sodium chloride (NaCl) is included as a dry release agent along with citric acid. Sodium chloride provided a nucleation site to change the ionic strength and release the gas from the solution more quickly.

It should be noted that the upper chamber 320, the lower chamber 330 and the fluid chamber 340 are depicted herein as being made up of separate parts that are connected to form the syringe 300. This part may be connected using methods known in the art. For example, the upper chamber is depicted herein as being formed from a side wall 325 having a closed top 322 with a port 327 for a plunger. The stopper 372 of the plunger is the shaft 37.
Connected to 4. The one-way valve 350 is a separate portion inserted into the open lower end 324 of the upper chamber. The lower chamber is depicted herein as being formed from a side wall 335 having an open upper end 332 and an open lower end 334. The upper end of the lower chamber and the lower end of the upper chamber work together to lock and secure the one-way valve in place. Here, the locking mechanism is a snap-fit facility comprising an upper end of a lower chamber having a cantilever snap 380 including an oblique surface and a stop surface. The lower end of the upper chamber has a latch 382 that engages with the cantilever snap.
Similarly, the lower chamber and fluid chamber are fitted with a ring-shaped seal.

9 and 10 are different views of exemplary embodiments of the injection device of the present disclosure. Syringe 500 is depicted here in a stored or unpressed state where the chemical reaction has not yet begun. FIG. 9 is a sectional view of the syringe engine, and FIG. 10 is a perspective view.

Again, the syringe contains a barrel 510 whose interior space is divided into three separate chambers.
The syringe begins at the top 502 of the barrel, with an upper chamber 520, a lower chamber 530 and a fluid chamber 54.
Includes 0. These three chambers are coaxial and are here depicted as having a cylindrical shape. The lower chamber 530 can also be considered as a reaction chamber.

In this embodiment, the upper chamber 520 is a separate portion located within the barrel 510. The barrel is exemplified here as an outer wall 512 surrounding the upper chamber. The upper chamber 520 is exemplified here with an inner side wall 525 and an upper wall 527. The shaft 574 and thumb rest I button 576 extend from the upper wall 527 of the upper chamber in a direction away from the barrel. Therefore, it can be considered that the upper chamber 520 forms the lower end portion of the plunger 570. Lower end 5 of the upper chamber
24 is sealed with a seal 528, ie, a membrane or partition so that the upper chamber has a sealed volume. Note that the inner wall 525 of the upper chamber is free to travel within the outer wall 512 of the barrel. The upper chamber moves axially with respect to the lower chamber.

The lower chamber 530 has a port 537 at its upper end 532. The upper end 53 of the tooth ring 580
It exists in 2. Here, the teeth surround the port. Each tooth 582 is an upper chamber seal 528
Illustrated herein as having a triangular shape with vertices towards, and each tooth horns inward towards the axis of the syringe. The term "tooth" is commonly used here to refer to any shape that can be punctured in the upper chamber seal.

The piston 560 is located at the lower end 534 of the lower chamber 530. The piston 560 is also present at the upper end 542 of the fluid chamber 540. Here, the piston 560 includes a balloon 568 in the lower chamber that communicates with the head 566 and the port 537 at the upper end. In other words, the balloon acts as a push surface for moving the head. The head 566 may be described as being below or downstream of the balloon 568, or the balloon 568 may be described as being located between the head 566 and port 537. The needle 505 is at the lower end 544 of the fluid chamber and at the bottom end 504 of the syringe. Balloons are appropriately made from non-reactive materials.

The top end 502 (ie, side wall) of the barrel includes a pressure lock 518 that, in cooperation with the top surface 526 of the upper chamber, locks the upper chamber 520 in place when sufficiently moved towards the lower chamber 530. The upper chamber 520 is illustrated here extending out of the outer wall 512. The top end 526 of the outer side wall is formed to function as a cantilever snap, and the top surface 526 of the upper chamber functions as a latch.

Alternatively, the top of the device may be formed with the pressure lock on the shaft close to the thumb rest and in cooperation with the top of the device, as depicted in FIG.

As mentioned above, the drying reagent is placed in the lower chamber 530, and the wet reagent (that is, the solvent) is placed in the upper chamber 52.
It is generally considered that it will be placed at zero. Again, the reagents in any of the chambers (s) may be encapsulated for easier handling during production. More specifically, it is conceivable that the reagents in the lower chamber will be located within the balloon 568.

Upper chamber 5 by pressing button 576 downward during the operation of the syringe of FIGS. 9 and 10.
20 is moved into the barrel towards the tooth ring 580. Upper chamber pressure on the tooth ring breaks the seal 528 and releases the contents of the upper chamber into the lower chamber 530. Here, it is considered that the gas generation reaction occurs inside the balloon 568. The increased gas pressure causes the balloon to inflate (ie, elongate). This pushes the head 566 towards the bottom end 504 of the syringe (note that the upper chamber will not be pushed out of the barrel due to the pressure lock). This again increases the volume of the lower chamber 530 and decreases the volume of the fluid chamber 540, that is, the volume ratio of the lower chamber to the fluid chamber increases.

There is an empty volume 507 that exists between the balloon 568 and the head 566. The incompressible gas can be located in this empty volume. The size of this empty volume may be changed as needed, for example to make the overall device longer.

Again, the upper chamber 520, lower chamber 530 and fluid chamber 540 may be made up of separate parts that are connected to form a syringe. FIG. 10 shows five parts (590, 592, 594) with the addition of balloons in the lower chamber and additional parts due to the upper chamber away from the outer wall.
Note that it is made from 596 and 598). However, in this embodiment, FIG.
It can also be created from even fewer parts, such as. For example, the balloon may be located near the ring of teeth.

11, 12 and 13 are different views of a third exemplary embodiment of the injection device of the present disclosure. In this embodiment, mixing of the chemical reagents is initiated by pulling the handle of the plunger away from the barrel, rather than towards the barrel as in the embodiments of FIGS. 7-10. FIG. 11 is a side view of the syringe in a stored state. FIG. 12 is a perspective view of the syringe engine in the stored state. FIG. 13 is a perspective view of the syringe engine in an operating state, i.e., when the handle is pulled upward from the barrel of the syringe.

Syringe 700'includes barrel 710', whose interior space is divided into three separate chambers. The syringe begins at the top of the barrel 702'and includes an upper chamber 720', a lower chamber 730' and a fluid chamber 740'. These three chambers are coaxial and are here depicted as having a cylindrical shape. The lower chamber can also be considered as a reaction chamber.

In this embodiment, the plunger 770'is inserted into the upper end 722' of the upper chamber. In the storage state, the shaft 774'passes through the upper chamber from the lower end 724' to the upper end 722'and passes through the upper surface 726'of the upper chamber. Seal 728'is located at the top of the shaft exiting the upper chamber. The thumb rest 776'at the upper end of the shaft is outside the upper chamber. The stopper 772'at the lower end of the shaft cooperates with the pedestal 716'in the barrel so that the upper chamber has a sealed volume. For example, the top surface of the stopper may have a diameter larger than the bottom surface of the stopper. The pedestal 716'may be considered to be at the lower end 724' of the upper chamber and may be considered to be at the upper end 732' of the lower chamber.

The piston 760'is located at the lower end 734' of the lower chamber. The piston 760'also exists at the upper end 742' of the fluid chamber 740'. As illustrated herein, the piston 760'is formed from at least two parts, a push surface 762' and a head 766'.
An empty volume 707'may be present. Other aspects of this piston are similar to those described in FIG. Again, the piston can move within the barrel in response to pressure. Lower room 730'
Can be described as defined by a pedestal 716, a continuous side wall 712'of the barrel and a piston 760'. The needle 705'is at the lower end 744'of the fluid chamber and at the bottom end 704' of the syringe.

During the operation of the syringes of FIGS. 11-13, the drying reagent was placed in the lower chamber 730'as described above.
It is generally considered that the wet reagent (ie solvent) will be placed in the upper chamber 720'.
Referring now to FIG. 11, pulling the plunger 770'upward (ie, away from the barrel) separates the stopper 772'from the pedestal 716'. This is the upper room 72
It creates fluid communication between 0'and lower chamber 730'. The reagents in the upper chamber travel around the stopper into the lower chamber (reference number 717'). Then, a gas generation reaction occurs in the lower chamber 730'.
The gas pressure pushes the piston 760'towards the bottom end 704' of the syringe. In other words, the volume of the lower chamber increases and the volume of the fluid chamber decreases, that is, the volume ratio of the lower chamber to the fluid chamber increases. One further advantage of this embodiment is that as the reagents begin to generate gas, the pressure generated keeps the plunger 710' further out of the upper chamber, pushing more reagents out of the upper chamber 7
It will help push from 20'to the lower chamber 730'and promote gas generation.

With reference to FIG. 12, barrel 710'has three different parts 790', 792', 79.
It is drawn as if it were composed of 4'. Seal 738'is also located between the parts that make up the lower chamber and the fluid chamber.

14 and 15 are cross-sectional views of one embodiment of another exemplary embodiment of the injection device of the present disclosure. In this embodiment, the liquid reagent (ie, solvent) is encapsulated in a capsule and destroyed when the button is pressed. FIG. 14 shows this engine before the button is pressed. FIG. 15 shows the engine after the button is pressed.

First, referring to FIG. 14, the top end 1002 of the syringe 1000 is shown. Reaction chamber 1030 contains capsules 1038 and drying reagents (s) 1039. Here, the capsule is mounted on ledge 1031 above the desiccant (s).
The push surface 1062 of the piston 1060 is located at the lower end of the reaction chamber. Piston head 1
066 is also visible and is located at the upper end 1042 of the fluid chamber 1040. The button / plunger 1070 is located above the capsule. Seal 1026 has button 1070 and capsule 10
It may exist between 38 and 38. The barrel includes a safety snap 1019 to prevent the button from falling off the end of the barrel.

If necessary, the portion of the reaction chamber containing the capsule may be considered as the upper chamber, and the portion of the reaction chamber containing the drying reagent (s) may be considered as the lower chamber.

Referring now to FIG. 15, when the button 1070 is pressed, the capsule 1038 is destroyed and the solvent and the drying reagent (s) are mixed. This produces a gas that pushes the piston 1060 downwards to eject the fluid from the fluid chamber 1040. By pressing the button, it engages with a pressure lock 1018 that subsequently prevents the button from being pushed upward by gas pressure.

The embodiment in the figure above is exemplified as an automatic syringe. The automatic syringe is typically held in the user's hand, has a cylindrical Scherrer equation, and has a relatively fast injection time of 1 to 30 seconds. It should be noted that the ideas embodied in the above figure may also apply to other types of injection devices such as patch pumps. In general, patch pumps have a flatter Scherrer equation compared to syringes, and typically also have delivery times longer than 30 seconds. Advantages of using chemical gas generation reactions in patch pumps include the need for small volumes, flexibility in morphology / shape and the ability to control delivery rates.

FIG. 16 is a diagram of a typical bore syringe 1200. Borus syringes include a reaction chamber 1230 and a fluid chamber 1240 located within housing 1280. As shown here, the reaction chamber and the fluid chamber are located next to each other, but this may be changed if necessary.
The reaction chamber 1230 is formed from the side wall 1235. The fluid chamber 1240 is also formed from the side wall 1245. The reaction chamber and fluid chamber are fluidly connected by flow paths 1208 at the first end 1202 of the device. The fluid chamber 1240 is located at the opposite second end of the housing, 1204.
Includes a discharge port 1246 connected to a needle 1205 located at. The needle 1205 extends from the bottom 1206 of the housing.

The reaction chamber is divided into a first compartment and a second compartment by a partition (not visible). At that time, the first compartment is similar to the lower chamber described above, and the second chamber is similar to the upper chamber.

The reaction chamber can be thought of as an engine that ejects the fluid in the fluid chamber. At that time, it is conceivable that the gas generation chemical reaction can be initiated by breaking the seal between the first compartment and the second compartment. The dividers can be broken, for example, by bending or folding the patch pump housing or by pushing a designated position on the housing. This mixes the reagents. The speed at which the chemicals are mixed is not a major concern as the desired delivery time is longer. The pressure may rise and act on the piston (invisible) in the fluid chamber, causing the fluid to exit through the outlet. It is considered that the volumes of the reaction chamber and the fluid chamber do not change significantly in the present embodiment.

17 and 18 are perspective views of another exemplary embodiment of the patch pump. In this embodiment, the reaction chamber / engine 1230 is located above the fluid chamber 1240. Needle 1205
Extends from the bottom 1206 of the housing 1280. In this embodiment, reaction chamber 123
0 includes the flexible wall 1235. The fluid chamber 1240 also includes a flexible side wall 1245. The flexible wall of the reaction chamber is close to the flexible side wall of the fluid chamber. The reaction chamber and the fluid chamber are not fluidly connected to each other in this embodiment. Instead, as gas is generated in the reaction chamber,
It is conceivable that the volume of the reaction chamber will increase. The flexible wall 1235 of the reaction chamber will compress the flexible side wall 1245 of the fluid chamber and allow the fluid in the fluid chamber to exit through the outlet 1246. In other words, as the reaction chamber expands and the fluid chamber distributes the fluid, the volume ratio of the reaction chamber to the fluid chamber increases over time. It should be noted that a relatively constant volume is required in this embodiment so that increasing the volume of the reaction chamber causes compression of the fluid chamber. This can be achieved, for example, by including a hard backing material on the opposite side of the reaction chamber to the flexible wall or by making the housing out of a relatively hard material.

FIG. 19 illustrates another exemplary embodiment of an apparatus (here, a syringe) that can be used to deliver a viscous fluid that uses a chemical reaction between reagents to generate a gas. Syringe 1300 is depicted here in a stored or unpressed state where the chemical reaction has not yet begun. Needles are not included in this figure.

Syringe 1300 includes a barrel 1310 whose interior space is divided into three separate chambers. The syringe begins at the top of the barrel 1302 and includes a reagent chamber 1320, a reaction chamber 1330 and a fluid chamber 1340. These three chambers are coaxial and are here depicted as having a cylindrical shape. In this embodiment, the barrel of the syringe is formed from two different parts. The first portion 1380 includes a side wall 1312 that forms a reaction chamber and provides space 1313 for the reagent chamber. The side wall is open at the top 1302 for pushbuttons further described herein. The fluid chamber may be attached to the first part, second part 139
Made from 0.

The side wall 1312 of the first portion includes an internal radial surface 1314 that divides the first portion into an upper space 1313 and a reaction chamber 1330. The reaction chamber has an inner diameter of 1325, which is smaller than the inner diameter of 1315 in the upper space.

The reagent chamber is located within the upper space 1313 of the first portion and within a separate pushbutton member 1350 extending through the top end 1302 of the barrel. As illustrated herein, the pushbutton member is formed from a side wall 1352 that is closed by a contact surface 1354 at the outer end 1351 and forms an internal volume (ie, a reagent chamber) into which the reagent is placed. The sealing member 1356 (shown here as a 0-ring) is adjacent to the central portion on the outer surface 1355 of the side wall and engages the side wall 1312 in the upper space. The inner end 1353 of the side wall includes an edge 1358 extending outward from the side wall. The edge engages the inner stop surface 1316 on the barrel. The reagent chamber is depicted as containing the solvent 1306 in which the bicarbonate is dissolved.

The plunger 1370 is located between the reagent chamber 1320 and the reaction chamber 1330. The plunger 1370 is located at the inner end 1324 of the reagent chamber. The plunger includes a central body 1372 with a lug 1374 extending radially from it (shown here as four lugs, but the number can vary). The lug also engages the edge 1358 of the pushbutton member when the syringe is in its storage state. The lugs are formed by an angled surface 1376 such that the plunger 1370 rotates when the pushbutton member 1350 is pressed. Inner end 1 of the central body
373 includes a sealing member 1378 (denoted as an O-ring) that engages the side wall of the reaction chamber.

The reaction chamber 1330 includes a top end 1332 and a bottom end 1334. Another internal radial surface 1336 is located in the center of the reaction chamber, with the mixing chamber 1335 adjacent to the reagent chamber 1320 or the top 1332, and the reaction chamber with the mixing chamber 1335 and the arm / fitting 13.
Separate into 33. The orifice 133 in the internal radial surface is a second including the fluid chamber 1340.
Leads to the arm fitting 1333 that engages the portion 1390. The piston 1360 is located at the bottom end of the reaction chamber, i.e. at the end of the arm 1333. Dry reagent 1308 is located in the reaction chamber. Here, the drying reagent is citrate and is in the form of tablets. The drying reagent is
Here, it is drawn as being located on the inner radial surface, that is, in the mixing chamber. The gas permeable I liquid-solid impermeable filter 1337 may be present across the orifice.
The filter maintains any dry solid reagent and liquid in the mixing chamber to improve mixing.

Further, the compression spring 1395 is located in the mixing chamber and extends from the inner radial surface 1336 to the inner end 1373 of the plunger. A compression spring stores energy when compressed (ie, longer when it is unloaded). Since the pushbutton member 1350 and the plunger 1370 are fixed in place, the compression spring 1395 is compressed in the stored state. It should be noted here that the spring surrounds the desiccant. In another embodiment, the drying reagent may be attached to the inner end 1373 of the plunger.

Finally, the piston 1360 is also present at the upper end 1342 of the fluid chamber. Again, piston 13
The 60 may move within the barrel in response to the pressure generated in the reaction chamber. The piston has a push surface 1
It can also be described as having a 362 and a stopper 1364.

The plunger sealing member 1378 separates the liquid reagent in the reagent chamber 1320 from the drying reagent in the reaction chamber 1330. The liquid 1306 is exemplified as being present in the pushbutton member, while the liquid can also be present in the barrel in the upper space 1313 around the plunger.

When the pushbutton member 1350 is pressed (up to the internal radial surface 1316), the plunger 1370 rotates. This pushes the plunger lug 1374 to the edge 135 of the pushbutton member.
Release from 8. Further, it is considered that the pushbutton member cannot be retracted from the barrel once it is pressed. This is, for example, a stop surface near the outer end of the barrel (
(Not shown) can be used.

If the plunger 1370 is no longer held in place by the pushbutton member, the compression spring extends to push the plunger 1370 into the pushbutton member 1350. The compression spring may be sized so that the plunger travels completely through the pushbutton member but does not push through the contact surface 1354 of the pushbutton member. The liquid 1306 present in the reagent chamber falls into the reaction chamber and comes into contact with the drying reagent 1308. The movement of the plunger into the pushbutton member is
It is intended that the contents of the reagent chamber be completely poured into the reaction chamber. This mechanism may also provide strong mixing of wet reagents with desiccants induced by spring action, initial chemistry, or both.

In some other embodiments, the spring also pushes at least some desiccant into the reagent chamber (ie, the internal volume of the pushbutton member). For example, the drying reagent may be attached to the inner end 1373 of the plunger and pushed upward by a spring.

FIG. 20 is a bottom view illustrating the inside of the push button member. As can be seen here, the inner surface 1357 of the side wall forming the pushbutton member includes four paths 1359 through which the lugs of the plunger can travel. FIG. 21 is a top view of the plunger 1370 showing a lug 1374 that can travel in the path of the central body 1372 and the pushbutton member. Comparing these two figures, the outer circle of FIG. 20 is the edge portion 1358 of the pushbutton member and has an outer diameter of 1361. The inner diameter 1363 of the pushbutton member is interrupted by four paths. The dotted circle indicates the outer diameter 1365 of the side wall outer surface 1355. The central body of the plunger has a diameter of 1375, which is smaller than the inner diameter of 1363 of the pushbutton member, with the lugs within the path. This allows the plunger to push the liquid in the pushbutton member out and around the central body. Note that the route does not have to be straight, as illustrated here. For example, the path may be bent to one side, i.e. spirally twisted. This may be desirable to add turbulence to the liquid reagent to improve mixing.

Mixing the solvent in the reaction chamber 1330 with bicarbonate and citrate produces gas 1309. Note that due to the movement of the plunger, the reagent chamber here can be considered part of the reaction chamber. Further note that the drying reagent 1308 in FIG. 19 can be considered as limiting access to orifice 1331. Once melted, the orifice is cleared and gas can enter the bottom end 1334 of the reaction chamber.

Once the critical pressure is reached, the piston 1360 travels through the fluid chamber 1340 and ejects fluid from the syringe. The needle 1305 of the syringe is visible in this figure.

In some other intended embodiments, the diameter of the plunger, including the lug, is smaller than the inner diameter of the pushbutton member, 1363. In other words, the path need not be on the inner wall of the pushbutton member. In such an embodiment, the barrel sidewall will provide a surface that holds the plunger in place until the pushbutton is pressed to rotate the plunger. The shape and movement of the plunger would then cause turbulence in the liquid as the wet reagent flowed through the lag into the reaction chamber. A handle extending into the reagent chamber may be attached to the plunger, or in other words, the handle may be attached to the outer end of the plunger. The stalk may be shaped to cause turbulence and improve mixing.

A duct with an opening can be utilized to accelerate gas generation in the chemical engine, as shown in FIG. At conduit 3700, flow 3703 is directed into the conduit at the inlet and then drains into the reaction chamber through multiple openings 3705 (preferably five or more openings). A conduit with an opening (co) in which the reaction chamber comprises a powder in which the flow from the opening is in direct contact with the powder.
The nduit-with-apertures) configuration is particularly advantageous. For example, an acidic solution (preferably a citric acid solution) flows through a conduit through an opening through which it contacts and agitates solid bicarbonate particles. In some preferred embodiments, the plunger (such as a spring-loaded plunger) pushes the liquid solution through the conduit. In some cases, the conduits contain at least partially dissolved solids (preferably solid bicarbonates) as the solution flows through the conduits, which further improves dissolution and further allows them to pass through the openings into the reaction chamber. It can provide the dual benefits of both the generation of gas bubbles in the conduit that enhance the mixing as it enters. Any of the devices described herein for adding a solution to the reaction chamber may be used to direct the fluid into this conduit.

It is also possible that the speed of injection can be adjusted by the user. One way to do this would be to control the speed at which the drying and wet reagents are mixed. this is,
It will regulate the speed of gas generation chemical reactions, and thus the speed at which the force pushing the piston is generated. This can be achieved, for example, by adjusting the size of the opening between the reagent chamber and the reaction chamber. For example, an adjustable opening can be placed under the plunger. The opening is (
It will have a minimal size (to accommodate the spring), but otherwise it can be adjusted. Another way to control the speed of injection would be to control the size of the reaction chamber.
This will regulate the pressure generated by the chemical reaction (because the pressure is the force per area). For example, the side walls of the reaction chamber can be moved inward or outward to change the volume of the reaction chamber as needed. Alternatively, the internal radial surface 1336 is an orifice 1331.
It may include an adjustable opening to change the speed at which the gas can enter the bottom end of the reaction chamber and push the piston 1360. Both of these methods can be controlled by a scale on the syringe, where the speed of injection can be mechanically adjusted by the user as needed. This will allow the speed of "flexible" injections to be adjusted. Like the other features described herein, this feature of user-controlled adjustable speed is a general feature that can be applied to any of the devices described herein.

It is also possible that there may be a gas permeable liquid-solid impermeable filter that separates the piston from the lower chamber in the injection device described herein. At that time, the dry powder was found to adhere to the sides of the chamber in some situations. As the piston moves, the residual solvent drops below the powder level to prevent further chemical reactions. It is believed that the filter should maintain any dry solid reagents and liquids in the lower chamber to improve mixing.

Suitable materials for the injection devices of the present disclosure are known in the art as methods for making injection devices.

Gas-generating chemistries, in contrast to springs, which only store energy when compressed,
Used to generate "demand-based" forces. Most automatic syringes hold the spring in a compressed position during "shelf" storage, causing the component to fatigue and form over time. Another alternative to compressing springs in manufacturing is to provide a cocking mechanism that compresses the springs before use. This adds another step to the process for using spring-loaded devices. In addition, disabled users may have difficulty performing cocking steps. For example, many users of protein drugs are patients with arthritis or have other conditions that limit their physical fitness. The force required to initiate a gassing chemical reaction can be much weaker than required to start a spring-loaded device or to cock a spring in a spring-loaded device. In addition, the spring has a linear energy profile. The forces provided by gassing chemistries can be non-linear and non-logarithmic. The speed of the chemical reaction is (i) adjusting the particle size of the drying reagent, (ii) changing the particle shape of the drying reagent, (iii) adjusting the packaging of the drying reagent, (iv) mixing auxiliary device. And / or (v) can be controlled by changing the shape of the reaction chamber in which the reagents are mixed.

Note that silicone oil is often added to the barrel of the syringe to reduce the discharge (due to static friction) required to move the piston in the barrel. Protein agents and other agents can be adversely affected by contact with silicone oils.
Silicone treatment is also associated with protein aggregation. The forces generated by the chemical reaction avoid the need to apply silicone oil to the barrel of the syringe. In other words, there is no silicone oil in the barrel of the syringe.

If a solvent is used to form a medium for a chemical reaction between chemical reagents, any suitable solvent can be selected. Exemplary solvents include aqueous solvents such as water or salt water, alcohols such as ethanol or isopropanol, ketones such as methyl ethyl ketone or acetone, carboxylic acids such as acetic acid, or mixtures of these solvents. Surfactants may be added to the solvent to reduce surface tension. This can help improve mixing and subsequent chemical reactions.

The following examples are for the purpose of further exemplifying the present disclosure. The examples are merely exemplary and are not intended to limit the processes or equipment produced in accordance with the present disclosure to the materials, conditions or process parameters described therein.

A test device 1000 for performing an experiment is shown in FIG. A standard prefilled syringe 1040 was filled with 1 ml of fluid. Prefilled syringe 10 starting from the left of the figure
A standard stopper 1066 with a 27-gauge thin-walled needle 1006 attached to 40 with a length of 19 mm.
I fastened it with. The syringe 1040 functioned as a fluid chamber. The reaction chamber syringe 1030 was connected to a prefilled syringe. The piston rod 1064 and the push surface 1062
It was used to apply the force from the chemical reaction to the stopper 1066. The one-way pressure valve 1050 was used to allow injection of solvent from a second "syringe" syringe 1020 that functions as a reagent chamber. The equipment was fixed to the test jig 1010. A graduated pipette (not shown) was used to measure the volume vs. time delivered.

Example 1
Two fluids, water (1 cP) and silicone oil (73 cP), were tested. Water served as a low viscosity fluid and silicone oil served as a high viscosity fluid. Depending on the experiment, one of these two fluids was added to the prefilled syringe 1040. Reaction chamber syringe 1030 to 4
00 mg of NaHCO ₃ and 300 mg of citric acid were added as a dry powder. The syringe syringe 1020 was filled with either 0.1 ml, 0.25 ml or 0.5 ml of water. Water was injected into the reaction syringe 1030 (the volume of the reaction syringe was adjusted based on the volume delivered by the syringe syringe). Volume vs. time delivered and total delivery time were measured. The pressure was calculated using the Hagen-Poiseuille equation and it was assumed that there was a frictional force of 0.6 lbs between the stopper 1066 and the prefilled syringe 1040. Alternatively, the force on the prefilled syringe 1040 was determined by placing a load cell at the outlet. The results are shown in Table 1 and were based on at least 3 runs.

The chemical reaction syringe provided delivery of 1 mL of water in less than 5 seconds. The delivery time of the more viscous fluid depends on the volume of water injected. Surprisingly, the delivery time is faster when the volume of water is larger. This is surprising because water does not participate in the reaction and acts to dilute the reagents. Reaction kinetics, and CO ₂ production decrease as the reagent concentration decreases. This result shows the importance of dissolution reaction kinetics. Dissolution is faster for larger volumes of water. The viscous fluid can be delivered in 9 seconds with 0.5 mL of water. Therefore, in some preferred embodiments, the present invention, in some embodiments, the ratio of the volume of water in the chemical institution to the volume of the drug is less than 2: 1, preferably less than 1: 1, 0.5.
Less than 1: and in some embodiments in the range 1: 1 to 0.3: 1, 1.0 m
At least 20 cP, within 20 seconds, within 15 seconds, or within 10 seconds, using a chemical institution with a starting volume (prior to expansion) of less than l, in some embodiments ranging from 0.3 to 1.0 ml. Preferably at least 40 cP and in some embodiments about 70 cP
It provides delivery of virtually any solution (at least 0.5 ml or 0.5 to 3.0 mil or 1 ml) having a viscosity less than. Throughout this description, viscosity is measured (or defined) as viscosity at 25 ° C. and under delivery conditions.

FIG. 22 shows 0.1 ml (triangle), 0.25 ml (square) and 0.5 ml (diamond).
FIG. 5 is a graph showing a pressure vs. time profile for delivery of silicone oil when water is injected into the reaction chamber. This graph shows a nearly constant or diminishing pressure vs. time profile that could be obtained after a period of ascent, although the effect of volume expansion was more predominant for longer periods of time. These pressure vs. time profiles were not exponential. A constant pressure vs. time profile can allow slower, flatter delivery of high viscosity agents, as opposed to sudden exponential bursts near the end of the delivery cycle.

Example 2
Sodium chloride (NaCl) was used to increase the emission of gaseous CO ₂ from the reaction solution in the reaction chamber and to accelerate the increase in pressure. In control experiments, citric acid and NaHCO
₃ was placed in the reaction syringe. An aqueous solution of 1.15 M NaHCO ₃ was injected from the syringe syringe into the reaction syringe. The empty volume in the reaction syringe was kept constant throughout all experiments. In experiments demonstrating the idea, NaCl was added to the reaction syringe. A chemical reaction was used to deliver 1 ml of water or silicone oil from the prefilled syringe. Volume vs. time delivered and total delivery time were measured. The pressure was calculated using the Hagen-Poiseuille equation and it was assumed that there was a frictional force of 0.6 lbs between the prefilled plunger and the syringe. It should be noted that bicarbonate was present in the water injected into the reaction syringe so that gas could be generated even if the solid bicarbonate was not present in the reaction syringe itself. Table 2
The result is shown in.

Salts have helped to significantly improve delivery rates, especially for systems with smaller reagents. High viscosity fluids could be delivered in 6 to 8 seconds using a chemical reaction. This is significantly faster than can be achieved with standard automatic syringes that employ mechanical springs.

FIG. 23 shows the delivered volume vs. time profiles of Experiment Nos. 5 and 6 in Table 2. The high viscosity fluid was delivered in 20 seconds using a system with an exclusive area of less than 1 cm3. The delivery rate (ie, slope) was also relatively constant. The small occupied area allows for a variety of useful devices.

Example 3
Several different reagents were tested to show the effect of powder morphology and structure on the pressure profile. In this case, morphology refers to the surface area, shape and packaging of the molecules in the powder. The same bicarbonate (sodium bicarbonate) was tested. Three different morphologies were produced (as received, lyophilized by lyophilization of 1.15M solution, and lyophilized reagent in the reaction chamber packaged in "stratified" tablets. Tested (where stratification refers to the preferential placement of reagents in the reaction cylinder). In another example, Alka-Seltzer containing citric acid and sodium bicarbonate in the base metal was used.

The following reagents, as-received baking soda (NaHCO ₃ ), citric acid, lyophilized baking soda, alka-seltzer or as-received potassium bicarbonate (KHCO ₃ ) were used. Baking soda as received was also tested as a powder or in the form of tablets. The tablet form had a reduced surface area.

Freeze-dried baking soda was prepared by preparing 125 ml of saturated aqueous sodium hydrogen solution (1.1SM). The solution was poured into a 250 ml crystal dish and covered with a Kimwipe. The solution was placed in a lyophilizer, lowered to −40 ° C. and held for 2 hours. Vacuum was applied at 150 millitorr (mTorr) for 48 hours, leaving the temperature at −40 ° C. Alka-Seltzer Tablets (Kr
Effectent Antacid & Pain Relie by Oger
f) was crushed into a coarse powder using a mortar and pestle.

Baking soda tablets were prepared by pouring 400 mg of as-received baking soda powder into a die to produce tablets with a diameter of 1 cm. The powder was moved to rotate the die to give a uniform depth over 1 cm. The die was placed in the molding machine and held at a pressure of 13 tons for 1 minute. Tablets weighing 40 mg and 100 mg were crushed from 400 mg tablets.

Instruments and planning The test equipment described above was used. A 3 ml injection syringe was filled with 0.5 ml of deionized water. A 10 ml reaction syringe was connected to the injection syringe with a luer lock and valve and then tightened into the instrument. The load cell was attached to the plunger rod so that the reaction syringe plunger pressed against it during the test. This recorded the force exerted by the reaction while the fluid in the prefilled syringe was displaced.

Fluid from the prefilled syringe was displaced into the graduated syringe, which was videographed. It observed changes in fluid volume over time. The fluid is water (1 cP
) Or silicone oil (73 cP), which was displaced through a 27 gauge thin-walled prefilled syringe and had a volume of 1 ml (ml).

Changes in volume of the prefilled syringe were obtained by measuring the volume distributed over time with two measurements, force on the prefilled syringe using a load cell, during each test. An average volume vs. time curve was plotted to show how each reaction changes volume in a prefilled syringe. A pressure vs. time curve using the Hagen-Poiseuille equation was provided by calculating the flow velocity from the volume vs. time curve. 94,219 Pa was added to account for friction in the prefilled syringe (which is equal to 0.6 lbs). Since this calculated the pressure inside the prefilled syringe (radius 3 mm), the hydraulic equation was used to calculate the pressure inside the reaction syringe (diameter 6.75 mm) (P ₁ A ₁ = P). ₂ A ₂ ). This was used to confirm the measurements made by the load cell.

Another pressure vs. time curve was generated by dividing by the area of the reaction plunger using the force at the load cell reading. We have found that this provides more reproducible data than the Hagen-Poiseuille calculation.

A pressure vs. volume curve was generated to determine how much the pressure changed with volume. The pressure used was calculated from the load cell readings. The reaction volume was calculated using changes in volume within the prefilled syringe. The volume (VR) of the reaction syringe is time t
It could be determined from the distributed volume (Vp) in the prefilled syringe in.

Finally, the reaction rate during fluid distribution, PR is the pressure calculated from the load cell, VR
Was obtained by using the ideal gas law, where R is the volume of the reaction syringe, R is the general gas constant (8.31 14 Jmol ^-1 K ^-1 ) and T is the temperature 298 K.

The test reference preparations were 400 mg baking soda, 304 mg citric acid and 0.5 ml deionized water as described in Example 1. This formulation is 4.76x10 assuming a yield of 100%
Produces -3 moles of CO ₂ . The raw materials for all tests are the same 4.7, assuming a yield of 100%
Formulated to produce 6x10-3 mol of CO ₂ . Four sets of tests were performed.

The first set used baking soda (BSAR) and lyophilized baking soda (BSFD) as received. Their relative amounts differed with a 25% increase. 304 mg of citric acid was also included in each formulation. Table 3A provides the target mass of baking soda for these tests.

The second set used baking soda and alka-seltzer as received. The amount of baking soda as received varied by a 25% increase. A stoichiometric amount of citric acid was added. Alka-Seltzer is only about 90% baking soda / citric acid. Therefore, the total mass of the added alka-seltzer was adjusted to obtain the required mass of baking soda / citric acid. Table 3B provides the target mass of each raw material for these tests.

The third set used baking soda as received and potassium bicarbonate as received. The mass of citric acid was maintained at 304 mg throughout the test. Due to the heavy molar mass of potassium bicarbonate (100.1 g / mol as opposed to 84.0 g / mol of baking soda), the same mole of CO
_More mass is needed to generate ₂ . Table 3C provides the target mass (in mg) of each ingredient for these tests.

The fourth set used baking soda tablets. A stoichiometric amount of citric acid was used. No other reagents were added. Table 3D provides the target mass (in mg) of each ingredient for these tests.

Results of the test First set: baking soda as received (BSAR) and lyophilized baking soda (BSFD).

The lyophilized baking soda powder looked coarser than the baking soda powder as received. The density was also lower (400 mg lyophilized powder accounted for 2 ml in the reaction syringe, while the as-received powder accounted for only 0.5 ml). Smaller volume of water (0.5) due to the volume of material
ml) was insufficient for complete contact with all of the lyophilized baking soda. Therefore, "1
In the "00%", "75%" and "50" experiments, the bicarbonate did not completely moisten, dissolve or react. Therefore, the fifth formulation was performed with the lyophilized sample inserted first. This was followed by citric acid and then the powder as received. This is "5
Labeled "0% BSAR 2nd". The formulation was allowed to contact the infused water first with the lyophilized powder and then with citric acid and the powder as received to dissolve. The time required to displace 1 ml of silicone oil is listed in Table 3E.

The volume vs. time graph can be seen in FIG. 100% freeze-dried powder is 1 at first
00% faster than the powder as received, but seemed to slow down over time. It took 10 seconds for the as-received powder to displace 1 ml and 14 seconds for the lyophilized powder. As expected, trials with mixed amounts were found to have a time between the two extrema.

A pressure vs. time graph is given in FIG. Formulations with 100% BSAR are 100%
It showed a maximum pressure close to 100,000 Pa, which is higher than that of BSFD. By comparison,"
By using "75% BSAR", faster pressure increase and slower decay were given. For ease of comparison, pressures were normalized and plotted in FIGS. 26 and 27 (two different periods).

100% BSAR had an initial slow reaction rate compared to 75% BSAR and 50% BSAR formulations. This suggests that the lyophilized baking soda (BSFD) dissolves and reacts faster, which is seen in FIG. However, FIG. 21 shows that lower maximum reaction pressures are obtained as the lyophilized baking soda content increases. Due to the low density of lyophilized powder, 200 mg of lyophilized baking soda occupies 1 ml of space, so 0.5 ml of deionized water cannot contact all materials before the generated gas moves the plunger. , Dry powder sticks to the side of the chamber and remains, all freeze-dried baking soda does not react and less C
O ₂ was generated. For the 100% BSFD trial, it was estimated that only a quarter of the reagents were dissolved. This phenomenon can be reduced by changing the chamber equipment, for example, when a gas generating chemical reaction occurs in a rigid chamber, where CO ₂ generated to push the plunger is diffused through the filter.

In a second trial of 50% BSAR, if lyophilized baking soda was added first, followed by citric acid and baking soda as received, many powders remained solid, resulting in low pressure. The low initial reaction was most likely due to 0.5 ml of water diffusing through 1 ml of lyophilized baking soda powder before reaching and dissolving citric acid. This test was the closest attempt to provide a constant pressure profile within this group.

The maximum pressure obtained was at a CO ₂ volume of about 0.8 ml for the 50% BSAR and 75% BSAR formulations. These formulations also had the fastest rates in the pressure vs. time graph (see Figure 26). The remaining formulation had maximum pressure at about 1.2 ml of CO ₂ .

Interestingly, when looking at FIGS. 23 and 24, "50% BSAR No. 2" showed a different pressure vs. time profile (Pa in FIG. 23), but 100% B in FIG. 24.
It had almost the same pressure vs. volume profile as SFD. Returning to Table 3E, "50% BSAR
For the second ", it took about 8 seconds longer to displace 1 ml of silicone oil, so the pressure curve was stretched compared to 100% BSFD and had different flow rates. This result shows the movement of the piston by including bicarbonates with two different dissolution rates, with different dissolution rates provided by their morphology and / or position in the reaction chamber.
And it is possible to reduce the pressure drop with volume expansion of the reaction chamber).
Table 3F shows the reaction rate of CO ₂ formation vs. time applied to y = ax ² + bx.

The 100% BSAR, 75% BSAR and 50% BSAR curves have approximately the same linear kinetics. "50% BSAR second" creates a quadratic polynomial. "100% BSFD" appears to be parametric, has the same linear velocity as 100% BSAR and the other two, then after 5 seconds the slope suddenly decreases and converges to "50% BSAR 2nd".

Second group: baking soda and alka-seltzer as received.

A volume-to-time graph of silicone oil in FIG. 28 and water as the fluid injected in FIG. 29 can be seen, respectively. The time required to displace each 1 ml of fluid is listed in Table 3G. The error in time measurement is estimated to be half a second.

The time for displacement of water is difficult to compare as they are all within 1 second of each other. The volume profiles of 100% BSCA, 25% BSCA and 100% Alka-Seltzer had the fastest time to displace 1 ml of silicone oil. 100% BSC
A seemed to start slowly and then speed up. 50% BSCA and 75
% BSCA was found to have the slowest time. They appeared to slow down as the displacement progressed.

A pressure vs. time graph of silicone oil in FIG. 30 and water as the fluid injected in FIG. 31 is given respectively. 100% BSCA had the slowest initial pressure rise. This was expected because Alka-Seltzer is prescribed to allow the rapid diffusion of water into the tablets. 75% BSCA and 50% BSCA had the second and third highest maximum pressures for silicone oils, respectively. However, these two formulations are 1 m
It took the longest to displace l silicone oil. Those pressures also had the slowest decay. This is likely due to increased friction within the syringe.

The curves for water in FIG. 31 are within reasonable error. However, they were higher than the pressure estimated by Hagen-Poiseuille, where the maximum pressure with the 100% Alka-Seltzer formulation was calculated to be 51,000 Pa. No significant friction was observed during the test.

A normalized pressure vs. time graph of silicone oil is provided in FIG. The pressure damping rates of the silicone oil are provided in Table 3H.

For silicone oils, 100% BSCA and 75% BSCA have the same normalized pressure increase but different reductions. As explained above, the 75% BSCA may have undergone greater friction, slowing the change in volume and holding the pressure longer. The same was true for 50% BSCA and had the same attenuation as 75% BSCA. Surprisingly, the 50% BSCA pressure increase fits just between 100% BSCA and 100% Alka-Seltzer. This may indicate that friction does not affect the pressure increase. 100% Alka-Seltzer and 25% BSCA had the same pressure profile with the fastest pressure increase and fastest decay. 100% BSCA also appeared to have the same attenuation as these two formulations.

For water, higher alka-seltzer ratios to BSCA were found to result in relatively small pressure damping. 100% Alka-Seltzer has a fast pressure increase but decays quickly as well as 100% BSCA "and 75% BSCA, but 25% BS.
CA and 50% BSCA had a fast pressure increase and less pressure decay than other formulations.

For silicone oil, 100% Alka-Seltzer, 50% BSCA and 75% BS
All CAs were maximal in a CO ₂ volume of about 1.2 ml. 25% BSCA is about 0
.. It was the maximum at 8 ml. 100% BSCA did not reach maximum pressure up to about 1.6 ml. This was slightly different from the "100% BSAR" in the first set of tests, which used the exact same formulation but reached its maximum pressure with a CO ₂ volume of 1.2 ml.

Table 3I shows the reaction rates for CO ₂ production during injection of silicone oil applied to y = ax ² + bx.

All formulations except 100% Alka-Seltzer formed a linear reaction rate for the silicone oil. High friction 75% BSCA and the pre-filled syringe was used to test the 50% BSCA results in high pressure, which might have reduced the reaction rate ^3x10 -5 mol / s. 100% BSCA and 25% BSCA ^{is, 4x10} -5 mol /
It had the same reaction rate in s. 100% Alka-Seltzer resulted in a quadratic polynomial. Initially it had the same kinetics as other formulations, but the slope decreased in the last few seconds. When the reaction was complete, the solution was much thicker than the other formulations.

100% BSCA is freeze dried sodium bicarbonate, was slightly slower in the difference ^1x10 -5 mol / sec than experiments before using 100% BSAR (see Table 3F). This may have resulted in a slower time to displace the silicone and, in some cases, a maximum pressure at a larger CO ₂ volume at 1.6 ml.

Third set: baking soda as received and potassium bicarbonate as received.

A volume vs. time graph for silicone oil can be found in FIG. The time required to displace each 1 ml of fluid is listed in Table 3J.

100% KHCO ₃ was the fastest to displace 1 ml of silicone in 6.33 seconds. The 100% BS and 50% BS were displaced at the same volume at 8.00 seconds.

A pressure vs. time graph is given in FIG. The pressure damping rates of silicone oils are provided in Table 3K.

The other two formulations had a maximum pressure of about 300,000 Pa, while the 100% BS formulation only reached a maximum pressure of about 250,000 Pa. 100% KHCO ₃ and 50
The% BS formulation (each containing potassium bicarbonate) continued to increase pressure for several seconds after 100% BS reached its maximum. The 50% BS formulation initially had lower pressure as expected, but after 6 seconds it was able to maintain higher pressure compared to 100% KHCO ₃ . This result showed that a mixture of sodium bicarbonate and potassium bicarbonate could produce higher pressure and slower decay.

The 100% BS had a peak pressure somewhere between 0.6 and 1.8 ml of CO ₂ .
The curves for 50% BS and 100% KHCO ₃ were different from the other pressure vs. volume graphs seen earlier. They continued to increase pressure at larger CO ₂ volumes, instead of maximizing and decaying at about 1.2 ml of CO ₂ volumes. 50% BS and 1
The 00% KHCO3 formulation was maximized with a CO ₂ volume of about 2.0 and 3.2 ml, respectively.

Table 3L shows the reaction rate applied to y = bx.

They, 100% BS has appeared to be a linear reaction rate is ^5x10 -5 mol / sec (the same speed as the above experiment). 100% potassium bicarbonate had twice the rate of baking soda.

Fourth set: baking soda tablets.
A volume vs. time graph for silicone oil can be seen in FIG. The time required to displace 1 ml of each fluid is listed in Table 3M.

For both silicone oil and water, 400 mg and 100 mg baking soda tablets and stoichiometric citric acid provided a near straight line. Packaging the baking soda in high-density tablets significantly reduced the reaction rate and thus increased the infusion time compared to other baking soda experiments. Table 3N shows the reaction rates applied to y = ax ² + bx.

For silicone oil, BS tablets 400mg ^showed linear kinetics as ^4x10 -6 mol / sec. The 100 mg baking soda tablet was linear for approximately 87 seconds until it suddenly stopped producing gaseous CO ₂ . The reaction rate of the 40 mg tablet was a quadratic polynomial and was very slow. It reaches the CO ₂ total 2x10 ^-5 mol, and possibly maintain a stable state in which there is some variation caused by CO ₂ that moves in and out of the solution. Due to the low reaction rate in water, only 400 mg tablets were used.

The results of Example 3 showed the ability to generate different pressure vs. time profiles when the dissolution kinetics were changed.

Example 4
A testing device was used to test silicone oil and 27 gauge thin wall needles. The stoichiometric reactions and results are shown in Table 4 below.

Example 5
The prototype test apparatus illustrated in FIG. 19 was tested using silicone oil. The prefilled syringe acted as a fluid chamber from which the fluid was ejected. A coupler was then used to join the prefilled syringe to the reaction chamber. The reaction chamber contained the mixture. A sheet of filter paper was placed in the reaction chamber to cover the orifice to the arm. The spring was then placed in the mixing chamber.
A plunger was then used to separate the desiccant in the reaction chamber from the moist liquid. The next part was a pushbutton, which contained an internal volume for the liquid reagent. For pushbuttons
Included holes (not visible) used to fill the volume with liquid reagents. Screws were used to fill the holes in the pushbuttons. A lid was mounted over the pushbutton to provide a structural support and also to surround part of the reaction chamber. Finally, a thumb press was placed on top of the lid for ease of compression. Both the reagent chamber and the reaction chamber were completely filled with liquid solution and dry powder, respectively.

Syringes are in vertical position (reagent chamber above reaction chamber) and horizontal position (two adjacent chambers)
Tested in both. The reagents and results are shown in Table 5 below.

Assuming sufficient mixing, potassium bicarbonate is a limiting reagent with an excess of 89 mg of citric acid. This assumption turned out to be false, as the liquid was found in the top chamber and the powder was found in the bottom chamber when disassembled. When the syringe was placed in a horizontal position, the chamber was completely filled and the silicone oil was displaced in 17 seconds. This illustrates that the device can work in any direction. This helps to allow patients to inject into their abdomen, thighs or arms, which is the most common position for self-injection.

Example 6
In the mixed bicarbonate test, the apparatus of Example 1 was used as a mixture of sodium bicarbonate and potassium bicarbonate 50:
It was modified to contain 50 mol of the mixture. The delivery of the silicone oil was adjusted to a faster time (less than 8 seconds) and the pressure vs. time was flat. The flow increased and then leveled off in less than 2 seconds. The use of mixed bicarbonate makes it possible to control the pressure profile for systems with different kinetics.

Example 7
It increases the gaseous emission of CO ₂ from use reaction solution nucleating agents to increase the release of CO ₂ into the reaction chamber, using sodium chloride (NaCl) in order to accelerate the increase in pressure. In control experiments, citric acid and NaHCO
3 was placed in the reaction syringe. An aqueous solution of 1.15 M NaHCO3 was injected into the reaction syringe. The empty volume in the reaction syringe was minimized throughout all experiments and was determined by the density of the powder. In an experiment demonstrating the idea of the present invention, NaCl was added to the reaction syringe. A chemical reaction was used to deliver 1 mL of water or silicone oil. Volume vs. time delivered and total delivery time were measured. The pressure was calculated using the Hagen-Poiseuille equation, taking into account the area of the plunger and assuming a frictional force of 0.6 lbs between the prefilled syringe plunger and the syringe.

Salts help to significantly improve delivery rates, especially for systems that use smaller amounts of reagents. High viscosity fluids can be delivered in 6 to 8 seconds, for example using a chemical reaction. This is significantly faster than can be achieved with standard automatic syringes that employ mechanical springs. The volume vs. time delivered for the least chemical reaction is shown. The viscous fluid was delivered in 20 seconds using a system with an occupied area of less than 0.5 cm ³ . The small occupied area allows for a variety of useful devices.

Example 8
Use of Reagents with Two Dissolution Rates to Change Pressure-to-Time Profile Reagents with two different dissolution rates were generated by combining NaHCO3 with two different morphologies (preferably different surface areas). For example, the mixture
It can be prepared using bicarbonate from different sources or by treating a portion of the bicarbonate before mixing with the untreated portion. For example, some may be lyophilized to increase surface area. Large surface area of NaHCO ₃ was produced by lyophilizing a 1.15 M solution. Reagents with two different dissolution rates were prepared as received sodium citrate / NaHCO ₃ and prepared sodium citrate / NaHCO 3 (Alka-Seltzer).
Was produced by mixing. This result shows the ability to generate different pressure vs. time profiles when the dissolution kinetics are changed.

Example 9
Minimization of pressure reduction using piston enlargement A chemical engine was created to deliver a fluid with a viscosity of 1 to 75 cP and a volume of 1 to 3 mL through a 27 gauge needle in less than 12 seconds. In the experiments of this example, the dry chemicals were premixed in a wide-mouthed bottle and then added to the reaction syringe (B). Reaction syringe
It consisted of either a 10 mL or 20 mL syringe. The plunger was pressed completely over the powder so that no additional empty volume was present. The solution was added to the reaction syringe and CO ₂ was generated, so the plunger rod pressed the PFS plunger to deliver the fluid. Six institutional formulations were considered, as shown in the table.

Force vs. time profiles of different chemical institutions are shown in Figures 40-42. Formulations 1 and 2 are 1 m
L fluid is used to deliver through a 27 gauge thin wall needle, i.e. standard PFS. Fluids with viscosities of 25 and 50 cP were tested. Faster delivery is achieved by increasing the amount of reagent. The use of potassium bicarbonate allows substantially fewer reagents to be used than if sodium bicarbonate was used.

Formulations 3, 4 and 5 were used to deliver 3 mL of 50 cP fluid through a 27 gauge thin wall needle. The target flow rate was greater than the target for formulations 1 and 2. In this case, simply expanding the reaction to a larger amount (formulation 3) results in a significant initial overshoot in force due to the rapid reaction. Overshoot was reduced by using 100% solid reagent (a mixture of citric acid and potassium bicarbonate in the reaction chamber) and water during the infusion. This method provided a steady state of CO ₂ because water dissolves potassium bicarbonate and makes bicarbonate ions available. Formulation 5 showed a flat delivery profile and delivered 3 mL of 50 cP fluid in 6.5 seconds.

Example 10
Addition of convective agent Addition of small amounts (eg <10 mg for 1 mL of engine) of slowly dissolving or insoluble particles substantially increases the rate of gaseous CO ₂ generation and produces the largest gaseous CO _2. However, it has been found to be effective in substantially increasing the power density of the engine. Surprisingly, we are working with a variety of slow-dissolving or insoluble particles, including diatomaceous earth, Expancel® (polyacrylonitrile hollow microspheres), calcium oxalate and crystalline oxalic acid. , Discovered the surface energy and surface topology of particles to have only a small effect. In this case, slowly dissolving is
It means that the particles are slowly associated with the reagents in the engine. The presence of these particles can be determined experimentally by dissolving the solid reagent to look for the presence of the particles or by determining the identity of the material present and comparing their solubility products. The density may be either lower or higher than water.

We see that these reagents work alone or in concert with gaseous CO ₂ leaving the fluid.
It is considered to constitute a mixing field similar to that found in fluidized beds. Mixing fields increase collisions between reagents and between convective agents and reagents. These increased collisions help to kinetically release trapped CO ₂ that may be present on surfaces or crevices, such as on the surface of a vessel or bicarbonate.

Our results show that these reagents do not primarily function as nucleating agents, which could be a minor factor. Reagents are useful in situations where the reaction chamber is fixed to a constant volume or allowed to expand. For example, in a constant volume environment, the pressure does not decrease and the solution is never supersaturated, as can be seen in pressurized sparkling beverages released to the atmosphere. Moreover, the addition of nucleated surfaces, such as porous aluminum, has no effect. The reagent must be present as particles in the engine.

The experiment was performed in one of two configurations.
Constant Volume: A constant volume configuration was used to compare different chemical reaction times. 2m reagent
The liquid reaction was added to the chamber by placing it in the reaction chamber and injecting it into the reaction chamber with the valve closed at the desired injection time using a syringe. The pressure was measured by a pressure transducer and the temperature was measured by a thermocouple. When the reaction was taking place, the pressure from the chamber was directed into the air cylinder through a small tube. The air cylinder was used as the equivalent of a piston / plunger in an actual injection system. For constant volume configurations, the air cylinder was first moved 1.5 inches to the end of the injection position of the 2 ml syringe and maintained that position throughout the test. This gave the total volume of the reaction chamber and the air cylinder was 9.9 ml. A load cell was used to measure the force as an adjunct to the pressure, which could be calculated from the pressure and the area of the piston in the cylinder. The advantage of using a constant volume configuration to see the initial chemical choices is
It allows good comparison of pressure vs. time profiles without having to consider the volume differences that the actual system would have.

Test conditions The following chemicals, sodium bicarbonate, potassium bicarbonate, citric acid, tartaric acid, oxalic acid,
Calcium oxalate, diatomaceous earth and Expancel® were tested as received. Anodized aluminum oxide was prepared by anodizing aluminum in oxalic acid to produce a porous surface structure and high surface energy.
The reaction was filled either in a reaction vessel or in a syringe as a solution. The reaction vessel is
Generally, the acid was included as a solid or solution, with or without any additives. The syringe contained a bicarbonate solution. The reactants (bicarbonate and acid) were weighed as powders on a stoichiometric ratio on a stoichiometric balance. The mass of the reactants is shown in the table below.
table. The mass of the reactant used in the test.

1 mL of water was used to dissolve the bicarbonates and to provide them with a medium in which the reaction could occur in the ChemEngine reaction chamber.
There were four different types of convective agents added to the chemical formulation, the nucleation surface was added to the reaction chamber, and external vibration was also added to the reaction chamber in a separate experiment.
1. 1. Water-insoluble-diatomaceous earth (DE) with high density
2. 2. Water-insoluble-polyacrylonitrile (PAN) hollow microsphere with low density 3. Water-insoluble-calcium oxalate 4. Highly soluble in water-sodium chloride and oxalic acid 5. Nucleation surface-anodized aluminum oxide 6. Mechanical Vibration All convective agents (1-4) were added to the chemical formulation as dry particles from 5 mg to 50 mg. A nucleation surface (anodized aluminum oxide) was added to the reaction chamber.

As shown in FIG. 43, all convective agents increased the rate of pressure accumulation beyond the reference formulation. In this case, the reference formulation is the same amount of potassium bicarbonate, citric acid and water, but no other chemicals are present. Mechanical vibrations also increased the rate of pressure buildup beyond the reference formulation. The nucleation surface had a negligible effect on the rate of pressure accumulation. The data in FIG. 43 is provided to show that the convective agent served to increase collisions between the reactants and between the reactants and the product, releasing CO ₂ into the gas phase at an increased rate. To. The data show that the addition of convective agent operated by a differentiated mechanism to increase the reaction chamber pressure more rapidly from the pressure of the nucleating agent. The data in FIG. 44 show that mechanical vibration (70 Hz from the Vibra-Fright® Controller) and convective agent have a similar effect on the speed at which the system displaces the plunger at a constant force.

FIG. 45 shows the surprising result that a relatively smaller amount of convection agent results in faster CO ₂ generation. In the experiment, the presence of about 10 mg of diatomaceous earth was 5 mg or 50 per ml.
It is shown to result in significantly faster CO ₂ generation than any of mg. Therefore, some preferred compositions include between 7 and 15 mg of convective or reagent.

Example 11
Power Densities The power densities of various chemical institutions were measured at either constant force or constant volume.

Constant force composition:
Constant force: A configuration similar to constant volume (described above) was used for constant force, but the platform on which the load cell was attached was mobile. The air cylinder was first closed so that the initial volume of the reaction chamber and the coupler were 2.3 ml. The air cylinder was moved 1.4 inches (3.56). This distance was chosen because it was the amount that the piston would have to advance to empty a standard 2 ml syringe. The pedestal is equivalent to first injecting 2 ml of 50 cP fluid with a standard 2 ml syringe in 27 gauge, TW needle in 8 seconds, 18
Pressurized to pounds. Further measurements were taken with a back pressure of 9 lbs. This is 1 ml of 50 cP
Equivalent to injecting fluid with a standard 1 ml syringe in 8 seconds using a 27 gauge, TW needle. The powder reactant was placed in the reactant chamber and the liquid reactant was placed in the syringe. The liquid reactant was injected into the chamber and the valve was closed. Pressure, force and temperature were measured until the air cylinder reached its travel distance determined using a LVDT (Linear Variable Differential Transformer) mounted on the pedestal. Table 46 shows the instruments.

The syringe labeled water in FIG. 46 could have been an aqueous solution containing either an acid or bicarbonate instead.

The test equipment can be applied to test almost any chemical institution. A chemical institution that is an integrated device may be tested by placing the entire device within a test instrument. When testing an integrated system that includes a fluid compartment, the average force may be measured directly or calculated using the Hagen-Poiseuille equation. Chemical institutions that are removable from the fluid compartment are first removed prior to testing.

In the table below, water was added to the powder mixed at a ratio of 1: 3 molar ratio of citric acid and bicarbonate.

Output density ratio:
Power densities were calculated for different back pressures and initial volumes. The time was measured starting at the start of the reaction, which is the time to mix the acid and carbonate with the solvent.

In our case, power density = mean force * distance to end of progression / (time of delivery * volume of initial reactant).
The volume used was the volume of the reactants after all the reactants were dissolved and CO ₂ escaped. Empty space not occupied by reactants or solvents in the reaction chamber is not taken into account in our calculations.

Example (line 1):
Power density = average force * displacement / time / volume of reactant 111,778 W / m ^ 3 = 99.3N * 3.56 cm * (0.01 m / cm) / 22.
59s / 1.4mL * (0.000001m ^ 3 / mL)
(The numbers are rounded for this example and do not exactly match the table.)
In each of the above experiments, the molar ratio of bicarbonate to citric acid is 3: 1 (generally, for all systems described in this application, preferred formulations are 2-4, more preferably 2. It has a molar ratio of bicarbonate to citric acid in the range 5 to 3.5). The invention can be characterized by a power density at room temperature as described above and measured and calculated at a nominal back pressure of 9 lbs (40 N). Under these conditions, the invention preferably is at least 50,000 W / m ³ , more preferably at least 100,000 W / m.
³ , more preferably at least 250,000 W / m ³ , more preferably at least 40
Having a power density upper limit 1,000,000W / ^{m 3} or about 900,000W / ^{m 3} at 0,000W / ^{m 3} and a part of the embodiments. Alternatively, the invention can be defined by comparison with a control formulation subject to the same conditions in terms of power density. The control formulation is 1 mL of water,
It contains 403 mg of citric acid and 529 mg of sodium bicarbonate. This control preparation
Suitable for a reaction chamber volume of about 2 mL, the power density of the control in chemical institutions larger or smaller than 2 ml should be tested with the control formulation adjusted in volume while maintaining the proportions of water, sodium bicarbonate and citric acid. Is. Again, as measured at a nominal back pressure of 9 pounds (40 N) and constant force, the chemistries of the invention preferably have a power density ratio of at least 1.4, more preferably at least 3, when compared to controls. In some embodiments, it has a maximum power density ratio of 10 or a maximum of about 5 or a maximum of about 4.4. In a preferred embodiment, the displacement begins within 2 seconds, more preferably within 1 second, from the moment the acid, carbonate and solvent (water) are mixed.

It should be noted that the term "control" does not imply conventional formulations as conventional formulations for chemical institutions have been further diluted. Controls are typically tested to full displacement,
If the complete displacement is not achieved within 30 seconds, the control is defined as the displacement within the first 30 seconds.
The present invention may have the following configurations.
[Invention 1]
A closed container with acid, bicarbonate, water, and a plunger,
An output density of at least 50,000 W / m ³ , as measured at a constant nominal back pressure of 40 N, with a mechanism adapted to mix the acid, the water, and the bicarbonate. molar ratio of 3: 1 containing sodium bicarbonate and citric acid and compared to the control with a citric acid concentration 403mg of of H _{2 O} 1g further characterized by at least 1.4 power density ratio of a chemical engine.
[Invention 2]
The chemical institution according to Invention 1, characterized by an output density of at least 250,000 W / m ³ .
[Invention 3]
The chemical institution according to Invention 1, characterized by an output density in the range of 100,000 W / m ³ to 1x10 ⁶ W / m ³ .
[Invention 4]
The chemical institution according to Invention 1, characterized by an output density ratio to the control in the range 1.4 to about 5.
[Invention 5]
The chemical institution according to any one of inventions 1 to 4, wherein at least 50 wt% of the bicarbonate is a solid.
[Invention 6]
The chemical institution according to any one of inventions 1 to 5, wherein the bicarbonate contains at least 50 wt% potassium bicarbonate.
[Invention 7]
The chemical institution according to any one of inventions 1 to 6, wherein the closed container further contains a convection agent.
[Invention 8]
The chemical institution according to any one of inventions 1 to 7, wherein the closed container contains 1.5 mL or less of a liquid.
[Invention 9]
The chemical institution according to any one of inventions 1 to 8, wherein the closed container has a total internal volume of 2 mL or less prior to mixing the acid and the carbonate.
[Invention 10]
The bicarbonate comprises a solid mixture of at least two particle morphologies, Inventions 1-9.
The chemical institution described in any one of the above.
[Invention 11]
The chemistry according to any one of the inventions 1 to 10, wherein the acid and the water exist as an acidic solution containing the acid dissolved in water, and the acidic solution is separated from the bicarbonate. organ.
[Invention 12]
The chemical institution according to any one of the inventions 1 to 11, wherein the acid and bicarbonate are present as solids, and the water is separated from the acid and bicarbonate.
[Invention 13]
Including an acidic solution containing an acid dissolved in water, bicarbonate, and a plunger, the acidic solution comprises a closed container separated from the solid bicarbonate and an opening located within the closed container to start. A chemical institution comprising a conduit configured to allow at least a portion of the acidic solution to be propelled through at least a portion of the opening.
[Invention 14]
The bicarbonate is in the form of fine particles, and the conduit is arranged within the solid bicarbonate so that it comes into contact with the solid bicarbonate fine particles when the solution is pushed through the opening. The chemical institution according to invention 13, comprising a tube having one end.
[Invention 15]
The chemical institution according to invention 13, wherein at least a portion of the bicarbonate is located inside the conduit in solid form.
[Invention 16]
The chemical institution according to any one of inventions 13 to 15, wherein the chemical institution comprises a spring configured to push the acidic solution through the conduit.
[Invention 17]
A closed container containing an acidic solution containing an acid dissolved in water, potassium bicarbonate, and a plunger, the acidic solution being separated from the potassium bicarbonate.
A chemical institution with a mechanism adapted to mix the acidic solution with the potassium bicarbonate.
[Invention 18]
The chemical institution according to invention 17, wherein the potassium bicarbonate is mixed with sodium bicarbonate.
[Invention 19]
A closed container containing an acidic solution containing an acid dissolved in water, solid bicarbonate particles, a solid particle convection agent, and a plunger, wherein the acidic solution is separated from the solid bicarbonate.
A chemical institution with a mechanism adapted to mix the acidic solution with the solid bicarbonate.
The solid particle convection agent is in the range of less than 50 mg per ml in the mixed solution, all other variables are kept constant and during the first 5 seconds when the acidic solution is combined with the solid bicarbonate. CO2 generation in the presence of 50 mg of the particle convection agent per ml
A chemical institution present at a concentration selected to be faster than the onset of, or at 5 mg to 25 mg per ml in a mixed solution.
[Invention 20]
A closed container containing an acidic solution containing an acid dissolved in water, solid bicarbonate particles, and a plunger, wherein the acidic solution is separated from the solid bicarbonate.
A chemical institution comprising a mechanism adapted to mix the acidic solution with the solid bicarbonate, wherein the solid bicarbonate particles contain a mixture of particle morphology.
[Invention 21]
The solid bicarbonate particles are derived from at least two different sources, a first source and a second source, and the first source is one or more of the following properties: That is, in terms of mass average particle size, surface area per mass, solubility in water at 20 ° C. as measured by the time it takes to completely dissolve a uniformly stirred solution in a 1 mol solution, the second source is The chemical institution according to invention 19, which differs by at least 20%.
[Invention 22]
It is a method of injecting liquid chemicals from a syringe.
A step of providing an airtight container comprising an acidic solution containing an acid dissolved in water, a bicarbonate, and a plunger, the acidic solution being separated from the bicarbonate, the acidic solution and said in the container. Bicarbonate limits the potential output density, the plunger separates the closed container from the drug compartment, with the step of providing a closed container.
The step of mixing the acidic solution and the bicarbonate in the closed container.
The acidic solution and the bicarbonate react to generate CO2 and power the plunger, which in turn pushes the liquid chemical from the syringe.
The pressure in the vessel reaches its maximum within 10 seconds after the start, and after 5 minutes the potential power density is less than 20% of the initial potential power density, and after 10 minutes the pressure in the closed vessel is A method comprising steps, which is 50% or less of the maximum pressure.
[Invention 23]
22. The method of invention 22, wherein the closed vessel further comprises a CO2 remover that removes CO2 at a rate at least 10 times slower than the maximum rate at which CO2 is generated in the reaction.
[Invention 24]
A reagent chamber having a plunger at the upper end and a one-way valve at the lower end, which allows the one-way valve to exit the reagent chamber.
A reaction chamber having the one-way valve at the upper end and a piston at the lower end,
A fluid having the piston at the upper end, wherein the piston moves in response to a pressure generated in the reaction chamber so that the volume of the reaction chamber increases and the volume of the fluid chamber decreases. A device with a chamber for delivering a fluid by a chemical reaction.
An apparatus in which the reaction chamber contains a dry acid powder and a release agent.
[Invention 25]
The device according to invention 24, wherein the acid powder is citrate and the release agent is sodium chloride.
[Invention 26]
A barrel with a reaction chamber and a fluid chamber, separated by a movable piston,
A device for delivering a fluid by a chemical reaction, comprising a heat source for heating the reaction chamber or a light source that illuminates the reaction chamber.
[Invention 27]
Invention 26, wherein the reaction chamber contains at least one chemical reagent that produces gas when exposed to light.
The device described in.
[Invention 28]
A process for delivering a highly viscous fluid by a chemical reaction
Including the step of initiating a gas generating chemical reaction in the reaction chamber of the device, said chamber containing a piston.
A process in which the gas moves the piston into a fluid chamber containing the high viscosity fluid to deliver the high viscosity fluid, and the high viscosity fluid is delivered in a constant pressure vs. time profile.
[Invention 29]
A device for delivering a fluid by a chemical reaction
A barrel containing a reagent chamber, a reaction chamber, and a fluid chamber.
The reagent chamber is a barrel located in a push button member at the top end of the barrel, and
A plunger that separates the reagent chamber from the reaction chamber,
A spring that is urged when the pushbutton member is pressed and pushes the plunger into the reagent chamber.
A device comprising a piston that separates the reaction chamber from the fluid chamber, wherein the piston comprises a piston that moves in response to pressure generated in the reaction chamber.
[Invention 30]
The pushbutton member comprises a side wall closed at the outer end by a contact surface, an edge extending outward from the inner end of the side wall, and a sealing member adjacent to a central portion on the outer surface of the side wall. The device according to invention 29.
[Invention 31]
29. The apparatus of invention 29, wherein the plunger comprises a central body having a lug extending radially from it and a sealing member on the inner edge that engages the side wall of the reaction chamber.
[Invention 32]
The device according to invention 31, wherein the inner surface of the pushbutton member includes a path for the lug.
[Invention 33]
The device of invention 29, wherein the reaction chamber is divided into a mixing chamber and an arm by the internal radial surface, the internal radial surface having an orifice, and the piston located at the end of the arm. ..
[Invention 34]
The device according to invention 33, wherein the mixing chamber includes a gas permeable filter covering the orifice.
[Invention 35]
An upper chamber with a seal at the bottom and
A port at the upper end, a ring of the tooth having a tooth facing the seal in the upper chamber at the upper end, and a lower chamber having a piston at the lower end.
A device for delivering a fluid by a chemical reaction including a fluid chamber having the piston at the upper end.
The upper chamber moves axially with respect to the lower chamber.
And the piston moves in response to the pressure generated in the lower chamber so that the volume of the reaction chamber increases and the volume of the fluid chamber decreases.
[Invention 36]
The device according to invention 35, wherein the piston includes a head and a balloon that communicate with the port.
[Invention 37]
The device according to invention 35, wherein the tooth ring surrounds the port.
[Invention 38]
The device according to invention 35, wherein the upper chamber travels in the barrel of the device.
[Invention 39]
The device according to invention 35, wherein the upper chamber is the lower end portion of the plunger.
[Invention 40]
The apparatus according to invention 38, wherein the plunger includes a pressure lock that locks the upper chamber in place in cooperation with the top end of the apparatus after being pressed.
[Invention 41]
Invention 3 the fluid chamber comprises a high viscosity fluid having a viscosity of at least 40 centipores.
8. The apparatus according to 8.
[Invention 42]
The apparatus according to invention 35, wherein the upper chamber contains a solvent.
[Invention 43]
Invention 3 the lower chamber contains at least two chemical reagents that react with each other to generate gas.
5. The apparatus according to 5.
[Invention 44]
The device according to invention 35, wherein the upper chamber, the lower chamber, and the fluid chamber are separate parts connected to create the device.
[Invention 45]
Upper room and
A lower chamber with a piston at the lower end and
A fluid chamber having the piston at the upper end,
A plunger comprising a shaft moving through the upper chamber, a stopper at the lower end of the shaft, and a thumb rest at the upper end of the shaft, the stopper cooperating with a pedestal to separate the upper chamber from the lower chamber. A device for delivering a fluid by a chemical reaction with a plunger.
Pulling the plunger separates the stopper from the pedestal to create fluid communication between the upper chamber and the lower chamber, and the piston increases the volume of the reaction chamber and the fluid chamber. A device that moves in response to pressure generated in the lower chamber so that its volume is reduced.
[Invention 46]
Invention 4 the fluid chamber comprises a highly viscous fluid having a viscosity of at least 40 centipores.
5. The apparatus according to 5.
[Invention 47]
The apparatus according to invention 45, wherein the upper chamber contains a solvent.
[Invention 48]
Invention 4 the lower chamber contains at least two chemical reagents that react with each other to generate gas.
5. The apparatus according to 5.
[Invention 49]
The device according to invention 45, wherein the upper chamber, the lower chamber, and the fluid chamber are separate parts connected to create the device.
[Invention 50]
The device of invention 45, wherein either the upper chamber or the lower chamber comprises an encapsulated reagent.
[Invention 51]
A reaction chamber divided into a first compartment and a second compartment by a partition, said first compartment containing at least two dry chemical reagents capable of reacting with each other to generate a gas.
The second compartment includes a reaction chamber containing a solvent and
A device for delivering a fluid by a chemical reaction, including a fluid chamber having a discharge port.
A device in which the fluid in the fluid chamber exits through the outlet in response to pressure generated in the reaction chamber.
[Invention 52]
The device according to the invention 51, wherein the pressure generated in the reaction chamber acts on a piston in the fluid chamber to discharge the fluid through the discharge port.
[Invention 53]
The device according to invention 51, wherein the reaction chamber is formed from a side wall, the fluid chamber is formed from a side wall, and the reaction chamber and the fluid chamber are fluidly connected at a first end of the device. ..
[Invention 54]
The reaction chamber includes the flexible wall in close proximity to the fluid chamber, and the pressure generated in the reaction chamber expands the flexible wall and presses against the flexible side wall of the fluid chamber, and the exhaust. The device of invention 51, wherein the fluid chamber is formed from the flexible side wall so that the fluid exits through the outlet.
[Invention 55]
The device according to invention 51, wherein the reaction chamber and the fluid chamber are surrounded by a housing.
[Invention 56]
The device according to invention 54, wherein the reaction chamber and the fluid chamber are adjacent to each other in the housing.
[Invention 57]
The device according to invention 54, wherein the needle extends from the bottom of the housing to fluidly connect to the outlet of the fluid chamber, and the reaction chamber is located above the fluid chamber.
[Invention 58]
An upper chamber having a fixed one-way valve at the lower end, said one-way valve allowing exit from the upper chamber.
A plunger that can proceed only through the upper chamber,
A device for delivering a fluid by a chemical reaction, comprising a lower chamber having the fixed one-way valve at the upper end and a piston at the lower end and a fluid chamber having the piston at the upper end.
A device in which the piston moves in response to pressure generated in the lower chamber so that the volume of the reaction chamber increases and the volume of the fluid chamber decreases.
[Invention 59]
Invention 5 the fluid chamber comprises a high viscosity fluid having a viscosity of at least 40 centipores.
8. The apparatus according to 8.
[Invention 60]
The apparatus according to invention 58, wherein the upper chamber contains a solvent.
[Invention 61]
58. The invention 58, wherein the piston is formed from a push surface at the lower end of the lower chamber and a head at the upper end of the fluid chamber, and optionally includes a rod connecting the push surface to the head. apparatus.
[Invention 62]
58. The apparatus of invention 58, wherein the plunger includes a thumb rest and a pressure lock that, after being pressed, collaborates with the upper chamber to lock the plunger in place.
[Invention 63]
The pressure lock is adjacent to the thumb rest and cooperates with the upper surface of the upper chamber.
2. The device according to 2.
[Invention 64]
The lower chamber is defined by the one-way valve, a continuous side wall, and the piston, and the one-way valve and the side wall are relative to each other such that the volume of the lower chamber changes only with the movement of the piston. The device according to invention 62, which is fixed.
[Invention 65]
The device according to invention 62, wherein the upper chamber, the lower chamber, and the fluid chamber are cylindrical and coaxial.
[Invention 66]
The device according to invention 62, wherein the upper chamber, the lower chamber, and the fluid chamber are separate parts that are connected to create the device.
[Invention 67]
The device according to invention 62, wherein the one-way valve supplies a balloon in the lower chamber, and the balloon pushes the piston.

Claims (44)

A reagent chamber having a plunger at the upper end and a one-way valve at the lower end, which allows the one-way valve to exit the reagent chamber.
A reaction chamber having the one-way valve at the upper end and a piston at the lower end,
A fluid having the piston at the upper end, wherein the piston moves in response to a pressure generated in the reaction chamber so that the volume of the reaction chamber increases and the volume of the fluid chamber decreases. A device with a chamber for delivering a fluid by a chemical reaction.
An apparatus in which the reaction chamber contains a dry acid powder and a release agent. The apparatus according to claim 1, wherein the acid powder is citrate and the release agent is sodium chloride. A barrel with a reaction chamber and a fluid chamber, separated by a movable piston,
A device for delivering a fluid by a chemical reaction, comprising a heat source for heating the reaction chamber or a light source that illuminates the reaction chamber. 3. The reaction chamber comprises at least one chemical reagent that produces gas when exposed to light.
The device described in. A process for delivering a highly viscous fluid by a chemical reaction
Including the step of initiating a gas generating chemical reaction in the reaction chamber of the device, said chamber containing a piston.
A process in which the gas moves the piston into a fluid chamber containing the high viscosity fluid to deliver the high viscosity fluid, and the high viscosity fluid is delivered in a constant pressure vs. time profile. A device for delivering a fluid by a chemical reaction
A barrel containing a reagent chamber, a reaction chamber, and a fluid chamber.
The reagent chamber is a barrel located in a push button member at the top end of the barrel, and
A plunger that separates the reagent chamber from the reaction chamber,
A spring that is urged when the pushbutton member is pressed and pushes the plunger into the reagent chamber.
A device comprising a piston that separates the reaction chamber from the fluid chamber, wherein the piston comprises a piston that moves in response to pressure generated in the reaction chamber. The pushbutton member comprises a side wall closed at the outer end by a contact surface, an edge extending outward from the inner end of the side wall, and a sealing member adjacent to a central portion on the outer surface of the side wall. The device according to claim 6. 6. The apparatus of claim 6, wherein the plunger comprises a central body having a lug extending radially from it and a sealing member on the inner edge that engages the side wall of the reaction chamber. The device of claim 8, wherein the inner surface of the pushbutton member includes a path for the lug. 6. The invention of claim 6, wherein the reaction chamber is divided into a mixing chamber and an arm by the internal radial surface, the internal radial surface having an orifice, and the piston located at the end of the arm. apparatus. The apparatus according to claim 10, wherein the mixing chamber includes a gas permeable filter covering the orifice. An upper chamber with a seal at the bottom and
A port at the upper end, a ring of the tooth having a tooth facing the seal in the upper chamber at the upper end, and a lower chamber having a piston at the lower end.
A device for delivering a fluid by a chemical reaction including a fluid chamber having the piston at the upper end.
The upper chamber moves axially with respect to the lower chamber.
And the piston moves in response to the pressure generated in the lower chamber so that the volume of the reaction chamber increases and the volume of the fluid chamber decreases. 12. The device of claim 12, wherein the piston comprises a head and a balloon communicating with the port. The device of claim 12, wherein the tooth ring surrounds the port. 12. The device of claim 12, wherein the upper chamber travels within the barrel of the device. The device according to claim 12, wherein the upper chamber is the lower end portion of the plunger. 15. The apparatus of claim 15, wherein the plunger comprises a pressure lock that locks the upper chamber in place in cooperation with the crown of the device after being pressed. 15. The apparatus of claim 15, wherein the fluid chamber comprises a highly viscous fluid having a viscosity of at least 40 centipores. The device according to claim 12, wherein the upper chamber contains a solvent. The apparatus according to claim 12, wherein the lower chamber contains at least two chemical reagents that react with each other to generate gas. 12. The device of claim 12, wherein the upper chamber, the lower chamber, and the fluid chamber are separate parts that are connected to create the device. Upper room and
A lower chamber with a piston at the lower end and
A fluid chamber having the piston at the upper end,
A plunger comprising a shaft moving through the upper chamber, a stopper at the lower end of the shaft, and a thumb rest at the upper end of the shaft, the stopper cooperating with a pedestal to separate the upper chamber from the lower chamber. A device for delivering a fluid by a chemical reaction with a plunger.
Pulling the plunger separates the stopper from the pedestal to create fluid communication between the upper chamber and the lower chamber, and the piston increases the volume of the reaction chamber and the fluid chamber. A device that moves in response to pressure generated in the lower chamber so that its volume is reduced. 22. The apparatus of claim 22, wherein the fluid chamber comprises a highly viscous fluid having a viscosity of at least 40 centipores. 22. The apparatus of claim 22, wherein the upper chamber contains a solvent. 22. The apparatus of claim 22, wherein the lower chamber comprises at least two chemical reagents that react with each other to generate gas. 22. The device of claim 22, wherein the upper chamber, the lower chamber, and the fluid chamber are separate parts that are connected to create the device. 22. The apparatus of claim 22, wherein either the upper chamber or the lower chamber comprises an encapsulated reagent. A reaction chamber divided into a first compartment and a second compartment by a partition, said first compartment containing at least two dry chemical reagents capable of reacting with each other to generate a gas.
The second compartment includes a reaction chamber containing a solvent and
A device for delivering a fluid by a chemical reaction, including a fluid chamber having a discharge port.
A device in which the fluid in the fluid chamber exits through the outlet in response to pressure generated in the reaction chamber. 28. The apparatus of claim 28, wherein the pressure generated in the reaction chamber acts on a piston in the fluid chamber to expel the fluid through the outlet. 28. The reaction chamber is formed from a side wall, the fluid chamber is formed from a side wall, and the reaction chamber and the fluid chamber are fluidly connected at a first end of the device. apparatus. The reaction chamber includes the flexible wall in close proximity to the fluid chamber, and the pressure generated in the reaction chamber expands the flexible wall and presses against the flexible side wall of the fluid chamber, and the exhaust. 28. The device of claim 28, wherein the fluid chamber is formed from the flexible side wall so that the fluid exits through the outlet. 28. The apparatus of claim 28, wherein the reaction chamber and the fluid chamber are surrounded by a housing. 31. The apparatus of claim 31, wherein the reaction chamber and the fluid chamber are adjacent to each other in the housing. 31. The device of claim 31, wherein the needle extends from the bottom of the housing to fluidly connect to the outlet of the fluid chamber, and the reaction chamber is located above the fluid chamber. An upper chamber having a fixed one-way valve at the lower end, said one-way valve allowing exit from the upper chamber.
A plunger that can proceed only through the upper chamber,
A device for delivering a fluid by a chemical reaction, comprising a lower chamber having the fixed one-way valve at the upper end and a piston at the lower end and a fluid chamber having the piston at the upper end.
A device in which the piston moves in response to pressure generated in the lower chamber so that the volume of the reaction chamber increases and the volume of the fluid chamber decreases. 35. The apparatus of claim 35, wherein the fluid chamber comprises a highly viscous fluid having a viscosity of at least 40 centipores. 35. The apparatus of claim 35, wherein the upper chamber contains a solvent. 35. The piston is formed from a push surface at the lower end of the lower chamber and a head at the upper end of the fluid chamber, and optionally includes a rod connecting the push surface and the head. Equipment. 35. The apparatus of claim 35, wherein the plunger includes a thumb rest and a pressure lock that, after being pressed, collaborates with the upper chamber to lock the plunger in place. 39. The device of claim 39, wherein the pressure lock is adjacent to the thumb rest and cooperates with the upper surface of the upper chamber. The lower chamber is defined by the one-way valve, a continuous side wall, and the piston, and the one-way valve and the side wall are relative to each other such that the volume of the lower chamber changes only with the movement of the piston. 39. The device of claim 39, which is fixed. 39. The apparatus of claim 39, wherein the upper chamber, the lower chamber, and the fluid chamber are cylindrical and coaxial. 39. The device of claim 39, wherein the upper chamber, the lower chamber, and the fluid chamber are separate parts that are connected to create the device. 39. The device of claim 39, wherein the one-way valve supplies the balloon in the lower chamber, the balloon pushing the piston.